Download or read book Role of Nuclear Hormone Receptor Co activator E6 associated Protein E6 AP in the Development of Breast Cancer written by and published by . This book was released on 2003 with total page 65 pages. Available in PDF, EPUB and Kindle. Book excerpt: Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivators modulate the biological activity of these hormone receptors. We have cloned an E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP) as a coactivator of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP may contribute to the development of breast cancer. We propose to explore this by developing animal models for overexpression and loss of function of E6-AP and then relate these observations to the clinical setting by studying the expression patterns of E6-AP in various human breast tumors. In this report, we report that we have successfully generated E6-AP overexpression models and an E6-AP null mouse line. Our data from these models suggest that overexpression of E6-AP in mammary gland results in impaired mammary gland development. Furthermore, loss of E6-AP expression results in an overly developed mammary gland compared to that of control mammary gland. These mice exhibit increased ductal branching and alveolar buds. However, the overexpression of transgene E6-AP and loss of function of E6-AP have no significant effects on the pregnant mammary glands. Additionally, we also show that E6-AP modulates the p53 expression in these animals. E6-AP possesses two independent and separable functions: coactivation and ubiquitin-protein ligase activity. Our data suggest that increased ductal branching and alveolar branching in E6-AP null mice are results of loss of ligase activity of F6-AP. To study the expression profile of E6-AP in human breast tumors, we examined 100 different human breast cancer biopsy samples. We found an inverse correlation between the expression of E6-AP and the expression of estrogen receptor-alpha in these tumors.

Download or read book Role of Nuclear Hormone Receptor Coactivator E6 Associated Protein E6 AP in the Development of Breast Cancer written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptors. We have cloned an E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP) as a coactivator of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP may contribute to the development of breast cancer. We propose to explore this by developing animal models for overexpression and loss of function of E6-AP and then relate these observations to the clinical setting by studying the expression patterns of E6-AP in various human breast tumor biopsies. In this progress report, we report that we have successfully generated an E6-AP overexpression model. In order to study the effect of loss of function of E6-AP on the normal breast development and breast tumor development, we have acquired an E6-AP null mouse line. These models will be helpful in understanding the role of E6-AP in the development and progression of breast tumors. Presently, we are in the process of breeding and analyzing the mammary gland development of both the overexpression and the loss of E6-AP expression models. Our data from these models suggest that overexpression of E6-AP in mammary gland results in impaired mammary gland development. Furthermore, loss of E6-AP expression results in an overly developed mammary gland compare to that of controls mammary gland. These mice exhibit increased ductal branching and alveolar buds. In order to study the expression profile of E6-AP in human breast tumors, we examined 56 advanced stage human breast cancer biopsy samples. We found an inverse correlation between the expression of E6-AP and the expression of estrogen receptor-alpha in these tumors.

Download or read book Ubiquitin Pathway Enzymes Coactivators of Nuclear Hormone Receptors and Their Role in the Development of Breast Cancer written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptors. We have cloned an E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP) and E2 ubiquitin-conjugating enzyme, UbcH7 as coactivators of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP and UbcH7 may contribute to the development of breast cancer. We have examined this possibility by studying the expression patterns of E6-AP, UbcH7 and estrogen receptor-alpha (ER) in various human breast cancer cell lines and breast tumor biopsy samples. Additionally, we have correlated the expression profile of E6-AP and UbcH7 with that of ER in breast tumor biopsies. Todate, we have examined 56 advanced stage human breast cancer biopsy samples for the expression profile of E6-AP, UbcH7 and ER. We found an inverse correlation between the expression of E6-AP and the expression of ER in these tumors. The Spearman Rank Correlation Coefficient is 0.38 and the p value is 0.004, indicating that this correlation is statistically significant. These data suggest a possible role of E6-AP in mammary gland development and tumorigenesis. However, we did not find any statistically significant eorrelation between the expression profile of UbcH7 and ER in these tumor samples. Presently, we are studying the expression profile of E6-AP, UbcH7 and ER in early and intermediate stage tumors. Another goal of this project is to create novel in vitro models in stable cell lines, which will overexpress coactivator proteins, E6-AP and UbcH7. In order to achieve this goal, we have already constructed the expression vectors for stable cell lines.

Download or read book Ubiquitin Pathway Enzymes Coactivators of Nuclear Hormone Receptor and Their Role in the Development of Breast Cancer written by Zafar Nawaz and published by [United States] : baylor coll of medicine houston tx. This book was released on 2004 with total page 58 pages. Available in PDF, EPUB and Kindle. Book excerpt: Steroid hormones, estrogen, and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptor. We have cloned an E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP) and E2 ubiquitin- conjugating enzyme, UbcH7 as coactivators of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP and UbcH7 may contribute to the development of breast cancer. We have examined this possibility by studying the expression patterns of E6-AP, UbcH7 and estrogen receptor- alpha (ER) in various human breast cancer cell lines and breast tumor biopsy samples. Additionally, we have correlated the expression profile of E6-AP and UbcH7 with that of ER in breast tumor biopsies. To study the expression profile of E6-AP and UbcH7 in human breast tumors, we examined 100 different human breast cancer biopsy samples. We found an inverse correlation between the expression of E6-AP and the expression of ER in these tumors. Furthermore, our data also demonstrate that 80% human tumors exhibited decreased level of E6-AP expression compared to that of normal mammary tissues. Furthermore, we found that E6-AP modulates the expression levels of ER both in vitro and in vivo. These data suggest a possible role of E6-AP in mammary gland development and tumorigenesis. However, we did not find any statistically significant correlation between the expression profile of UbcH7 and ER in these tumor samples. Another goal of this project is to create novel in vitro models in stable cell lines, which will overexpress coactivator proteins E6-AP and UbcH7.

Download or read book Role of E6 associated Protein e6 ap in Mammary Gland Development and Tumorigenesis written by Sivapriya - Ramamoorthy and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: E6-associated protein (E6-AP), which was originally identified as an ubiquitin-protein ligase, also functions as a co-activator that enhances the hormone-dependent transactivation of estrogen (ER) and progesterone (PR) receptors. To investigate the in vivo role of E6-AP in mammary gland development, we generated transgenic mouse lines that specifically overexpress either wild-type human E6-AP (E6-APWT) or the ubiquitin-protein ligase defective mutant E6-AP (E6-APC833S) in the mammary gland. Here we show that overexpression of E6-APWT results in impaired mammary gland development. In contrast, overexpression of E6-APC833S or loss of E6-AP (E6-APKO) increases lateral branching and alveolus-like protuberances in the mammary gland. We also show that the mammary phenotypes observed in the E6-AP transgenic and knockout mice are in large part due to the alteration of PR-B protein levels. RNAi-mediated knockdown of E6-AP in T47D breast cancer cells increased PR-B protein levels and stability. In vitro ubiquitination assay using purified E6-AP and PR-B reinforce these conclusions and demonstrate that E6-AP promotes PR-B turnover in an ubiquitin-dependent manner. Furthermore, we also show that E6-AP regulates progesterone-induced Wnt-4 expression by modulating the steady state level of PR-B in both mice and in human breast cancer cells. This novel mechanism appears to regulate normal physiology of the mammary gland and its dysregulation may prove to contribute importantly to mammary cancer development and progression. To test this hypothesis, we examined the E6-AP transgenic mice for tumor formation over a period of 6, 9, 12, 18 and 24 months. Our data shows that, unlike the E6-APWT mice that show normal phenotype, the E6-APC833S mice develop mammary hyperplasia at high penetrance (80%); with a median latency of 18 months. Our findings indicate that the inactivation of the E3-ligase function of E6-AP is sufficient to initiate the process of mammary tumor development. These findings strongly suggest that E6-AP may act as a tumor suppressor by down regulating the ER-alpha, PR-B and thereby their signaling pathways.

Download or read book Involvement of Steroid Receptor Coactivators Ubiquitin Pathway Enzymes in Mammary Gland Tumorigenesis written by and published by . This book was released on 2005 with total page 31 pages. Available in PDF, EPUB and Kindle. Book excerpt: Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptqrs. We have cloned and E3 ubiquitin-protein ligand-activated enzyme, E6-associated protein (E6-AP) as coactivators of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP may contribute to the development of breast cancer. We have examined this possibility by studying the expression patterns of E6-AP and estrogen receptor-alpha (ERalpha) in various human breast cancer cell lines breast tumor biopsy samples. Additionally, we have correlated the expression profile of RE-AP as that of ER in breast tumor biopsies. To date, we have examined 13 samples of invasive breast cancer (IBC), 12 samples of ductal carcinoma in situ (DCIS) and a tissue array with 36 different stages breast cancer samples by immunhistochemistry, and 19 samples by immunofluorescence. We found inverse correlation between the expression of RE-AP and the expression of ER in these tumors. Furthermore, RE-AP is down regulated in invasive breast tumors compared with their adjacent tissues, whereas the downregulation of RE-AP was not seen in DCIS. The downregulation of E6-AP is stage-dependent. These data suggest a possible role of RE-AP in mammary gland development and tumorigenesis. We also proposed to generate stable cell lines which overexpress either wild-type or liagse-mutated RE-AP and test its tumorigenecity both in vitro and in vivo. However, we weren't able to finish the task on time due to technical problems.

Download or read book Placat angaaende Oprettelsen af en Direction for Universitetet og de l rde Skoler i Danmark og Norge written by and published by . This book was released on 1950 with total page 2 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book EGF Regulation of Nuclear Co Activator AIB1 Function in Breast Cancer written by and published by . This book was released on 2002 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt: Various growth factor receptor pathways promote human breast tumorigenesis of hormone-independent tumors. The nuclear receptor coactivator AIBi (amplified in breast cancer 1) can be phosphorylated and regulated by growth factor-induced signaling pathways such as MAP kinase and IkB kinase. Our lab has found a splice variant of AIBl, called delta exon3 AIBl, which has a higher co-activating ability than the full-length protein. This study determined the ability of delta exon3 splice variant compared with AIBi in potentiating growth factor signaling and to determine the mechanism of this potentiation using a growth factor responsive promoter.

Download or read book Role of Nuclear Receptor Coactivators AIB 1 and SRC 1 in the Development of Breast Cancer written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Steroid hormones are involved in the development and growth of the breast cancer. Drugs which inhibit estrogen action are commonly used to inhibit breast cancer growth. Unfortunately, most advanced breast cancer become resistant to estrogen treatment. Recently, many steroid receptor coactivators have been discovered and found to potentiate the transcriptional activity of steroid receptors and enhance the expression of hormone response genes. SRC-1 family of coactivator, AIB1 is found amplified and/or over-expressed in breast cancer specimens. To evaluate the potential roles of SRC-1 family of coactivators in mammary tumorigenesis in vivo, we proposed to generated transgenic mice over-expression of AIB1 (SRC-3) in mammary glands. To target the expression of AIB1 1 in mammary gland, we placed the AIB1 1 transgene under the control of the MMTV-LTR promoter. Two lines of transgenic mice expressing AIB1 1 have been generated. Studies on these transgenic mice will help understanding the development and progression of breast cancer and provide molecular basis for design novel strategies to curb and ultimately cure breast cancer.

Download or read book Targeting of the Nuclear Receptor Coactivator Isoform DELTA3AIB1 in Breast Cancer written by and published by . This book was released on 2007 with total page 19 pages. Available in PDF, EPUB and Kindle. Book excerpt: AIB1 which stands for Amplified in Breast Cancer, codes for a protein that is a member of the steroid receptor coactivator (SRC) family. AIB1 is amplified in approximately 5-10% of breast cancers and the mRNA and protein overexpressed in>30% of breast cancers. AIB1 interacts with a superfamily of ligand activated nuclear receptors to potentiate transcriptional activity leading to upregulation of downstream target gene expression. An important finding was that an isoform of AIB1 (Delta3AIB1) is a significantly more effective coactivator of the estrogen receptor than AIB1 and is highly overexpressed in human breast cancer. Prior work in our lab showed that the downregulation of overall levels of AIB1 plus DELTA3AIB1, using a regulatable AIB1 directed ribozyme, resulted in reduced tumor growth in vivo. Overall, these data indicate a major role for AIB1 and its isoform DELTA3AIB1 in breast cancer development and growth. However the relative roles of AIB1 versus the more highly active DELTA3AIB1 in phenotypic changes in the breast has not been determined. In this investigation, we are developing a method to use siRNA directed at DELTA3AIB1 in order investigate its role in breast cancer and as a possible future therapeutic approach to breast cancer.

Download or read book Targeting of the Nuclear Receptor Coactivator Isoform Delta3Air in Breast Cancer written by and published by . This book was released on 2005 with total page 21 pages. Available in PDF, EPUB and Kindle. Book excerpt: Of particular interest to breast cancer was the discovery that an area of chromosome 20q, known to be frequently amplified in breast cancer, harbored the gene for AIB1. AIB1 which stands for "Amplified in Breast cancer" codes for a protein which is a member of the steroid receptor coactivator (SRC) family. AIB1 is amplified in approximately 5-10% of breast cancers and the mRNA and protein overexpressed in>30% of breast cancers. AIB1 interacts with a superfamily of ligand activated nuclear receptors including the estrogen receptor (ER) and progesterone receptor (PR) to potentiate transcriptional activity leading to upregulation of downstream target gene expression. An important finding was that an isoform of AIB1 (delta3AIB1) is a significantly more effective coactivator of the estrogen receptor than AIB1 and is highly overexpressed in human breast cancer. Prior work in our lab showed that the downregulation of overall levels of AIB1 plus delta3AIB1, using a regulatable AIB1 directed ribozyme, resulted in reduced tumor growth in vivo. Overall, these data indicate a major role for AIB1 and its isoform delta3AIB1 in breast cancer development and growth. However the relative roles of AIB1 versus the more highly active delta3AIB1 in phenotypic changes in the breast has not been determined.

Download or read book Defining the Functional Significance of Estrogen related Receptor Alpha in Breast Cancer written by Rebecca Anne Stein and published by . This book was released on 2008 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expression of estrogen-related receptor alpha (ERRalpha) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of this orphan nuclear receptor in tumor growth and progression, however, is yet to be fully understood. The significant homology between estrogen receptor alpha (ERalpha) and ERRalpha initially suggested that these receptors may have similar transcriptional targets. Using the well-characterized ERalpha-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ERalpha-ERRalpha cross-talk. Since a small molecule ligand has not been identified for ERRalpha, its transcriptional activity in these studies was induced using its known coactivator PGC-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) as a protein ligand (Schreiber et al. 2004). PGC-1alpha was used as a coactivator to highlight target genes modulated by activated ERRalpha. PGC-1alpha enhances the transcriptional activity of several nuclear receptors (NRs) and non-NR transcription factors resulting in the regulation of a variety of metabolic processes including lipid metabolism, mitochondrial biogenesis and oxidative metabolism (Huss et al. 2007, Lin et al. 2004). In order to isolate the ERRalpha-PGC-1alpha complex in these studies, we utilized a customized PGC-1alpha that selectively binds and activates only the ERRs (ERRspPGC1) (Gaillard et al. 2007). In addition to generating a host of novel ERRalpha target genes, this study yielded the surprising result that most ERRalpha-regulated genes are unrelated to estrogen-signaling. The relatively small number of genes regulated by both ERalpha and ERRalpha led us to expand our study to the more aggressive and less clinically treatable ERalpha-negative class of breast cancers. In this setting we found that ERRalphaa expression is required for the basal level of expression of many known and novel ERRalphaa target genes. Introduction of an siRNA directed to ERRalpha into the highly aggressive breast carcinoma MDA-MB-231 cell line dramatically reduced the migratory potential of these cells. Although stable knockdown of ERRalphaa expression in MDA-MB-231 cells had no impact on in vitro cell proliferation, a significant reduction of tumor growth rate was observed when these cells were implanted as xenografts. Our results confirm a role for ERRalpha in breast cancer growth and highlight it as a potential therapeutic target for estrogen receptor-negative breast cancer.

Download or read book Hormones Genes and Cancer written by Brian E. Henderson and published by Oxford University Press. This book was released on 2003-03-13 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hormonal carcinogenesis is an important and controversial area of current research. In addition to accelerating existing cancers, can hormones play the role of primary carcinogens? How do genetic factors influence hormone-related cancer risk? Hormones, Genes, and Cancer addresses these questions. Over the past few decades, cancer research has focused on external environmental causes(e.g., tobacco smoke, viruses, asbestos). With the advent of new genetic sequencing techniques, we are just now beginning to understand how the body's internal environment(i.e., the hormones and growth factors that determine normal development) influences cancer etiology and prevention. From molecular insights to clinical analyses, this volume provides state-of-the-art information on the complex interactions between hormones and genes and cancer. The epidemiology and molecular endocrinology of prostate, breast, uterine, ovarian and testicular cancer are detailed in this timely treatise.

Download or read book Insight Into Estrogen Action in Breast Cancer Via the Study of a Novel Nuclear Receptor Corepressor written by Esme Claire Hatchell and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: [Truncated abstract] Breast cancer is the cause of significant suffering and death in our community. It is now estimated that the risk of developing breast cancer for an Australian woman before the age of 85 is 1 in 8, with this risk rising for unknown reasons. While mortality rates from breast cancer are falling due to increased awareness and early detection, few new treatments have been developed from an advanced understanding of the molecular basis of the disease. From decades of scientific research it is clear that estrogen (E2) has a large role to play in breast cancer. However, the basic mechanism behind E2 action in breast cancer remains unclear. E2 plays a fundamental role in breast cancer cell proliferation and is highly expressed in breast cancers, thus, it is important to understand both E2 and its receptor, the estrogen receptor (ER). The ER is a member of the nuclear receptor (NR) superfamily. The NR superfamily consists of a large group of proteins which regulate a large number of homeostatic proteins together with regulator proteins termed coregulators and corepressors. SRA (steroid receptor RNA activator) is the only known RNA coactivator and augments transactivation by NRs. SRA has been demonstrated to play an important role in mediating E2 action (Lanz et al., 1999; Lanz et al., 2003) and its expression is aberrant in many human breast tumors, suggesting a potential role in breast tumorigenesis (Murphy et al., 2000). Despite evidence that an alternative splice variant of SRA exists as a protein (Chooniedass-Kothari et al., 2004), it has been conclusively shown that SRA can function as an RNA transcript to coactivate NR transcription (Lanz et al., 1999; Lanz et al., 2002; Lanz et al., 2003). The precise mechanism by which SRA augments ER activity remains unknown. However, it is currently hypothesized that SRA acts as an RNA scaffold for other coregulators at the transcription initiation site. Several SRA stem loops have been identified as important for SRA function, including structure (STR) 1, 5 and 7 (Lanz et al., 2002; Zhao et al., 2007). Previously, I sought to identify SRA-binding proteins using a specific stem-loop structure of SRA (STR7) that was identified as both important for its coactivator function (Lanz et al., 2002) and also as a target for proteins from breast cancer cell extracts (Hatchell, 2002). From a yeast E. Hatchell Abstract iii III hybrid screen using STR7 as bait, I identified a novel protein which was named SLIRP (Patent Number: WO/2007/009194): SRA stem-Loop Interacting RNA-binding Protein (Hatchell, 2002; Hatchell et al., 2006). '...' This thesis demonstrates that SLIRP modulates NR transactivation, provides mechanistic insight into interactions between SRA, SRC-1, HSP-60 and NCoR and suggests that SLIRP may regulate mitochondrial function. These studies contribute significantly to the growing field of NR biology, and contribute more specifically to the elucidation of estrogen action in breast cancer. Furthermore, it lays a strong and exciting foundation for further studies to evaluate SLIRP as a biomarker and potential therapeutic target in hormone dependent cancers.

Download or read book Principles of Molecular Oncology written by Miguel H. Bronchud and published by Springer Science & Business Media. This book was released on 2003-12-03 with total page 716 pages. Available in PDF, EPUB and Kindle. Book excerpt: At the midpoint of the 20th century, our knowledge of cancer was based on epide- ology and pathology, and treatment consisted of surgery and radiation therapy. At mid-century, Medawar and colleagues initiated the understanding of transplantation immunology, Farber described the first use of an antifolic drug to treat leukemia, and Jacobson and coworkers described the irradiation-protection effect of spleen cells. These observations opened the door to the development of chemotherapy and tra- plantation in the treatment of cancer. Despite the rapid development of these new disciplines, progress was usually based on empiric observations and clinical trials. The rapid advances in molecular biology at the end of the 20th century mark a new era in our knowledge of cancer. Molecular immunology, molecular genetics, mole- lar pharmacology, and the Human Genome Project are in the process of providing a level of understanding of cancer undreamed of in the past. Optimism is based on the firm belief that understanding at the molecular level will lead to better and earlier di- nosis, to new forms of treatment, and, most importantly, eventually to prevention of many types of cancer.

Download or read book The Nuclear Receptor Co Activator 5 is a Potential New Co regulator of the Estrogen Related Receptor alpha in Breast Cancer written by Amandine Laffitte and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Nuclear receptors are transcriptional factors that are essential for a wide range of biological processes. They are partly regulated through their interaction with co-regulatory proteins. Here, we focus on the orphan nuclear receptor ERRa and its potential new co-activator protein NCOA5. Using NCOA5 knockdown or overexpression via a lentiviral system, we investigated the role of NCOA5 in ERRa regulation in Her2-positive breast cancer cells and its effect on known targets of ERRa in this context, such as the ERBB2 amplicon transcription. We show that NCOA5 and ERRa can regulate each other, yet the precise mechanism remains to be elucidated. NCOA5 protein level affects ERR[alpha] transcription and protein level, also affecting the transcription of ERRa targets from the ERBB2 amplicon including the Her2 receptor itself. Modulation of NCOA5 levels leads to variation in cell proliferation and metabolism, thus revealing that NCOA5 is an important factor in the ERBB2 amplicon regulation." --

Download or read book Characterization of a Novel Nuclear Hormone Receptor Coactivator Uba3 and Its Function in Breast Cancer written by and published by . This book was released on 2003 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: We previously identified Uba3 as a nuclear hormone receptor coactivator that functions as part of the NEDD8 pathway to influence ER- and PR-mediated transcription. Although our previous model failed to demonstrate the connection between Uba3, the NEDD8 pathway, and transcription, we now have sufficient evidence to suggest the NEDD8 pathway is linked to ER- and PR-mediated transcription via the SCF E3 ligase complex. Here we show that Skpl can associate with ERalpha by co-immunoprecipitation, and with the p52 promoter by ChIP assay. We have investigated the mRNA expression of Uba3, PR, and ERa in several common tumor cell lines. We were not able to detect abnormal expression of huba3 mRNA in the breast cancer cell lines. Furthermore, we were unable to correlate hUba3 mRNA expression with PR and ERalpha expression across all cell lines. We also investigated in silico the potential that Uba3 mRNA expression may be regulated by estrogen and progesterone. Although possible binding sites for ER and PR were localized within the Uba3 promoter, we were not able to detect induction or repression of Uba3 mRNA by estradiol, and SERMs tamoxifen, and raloxifene, or progesterone.