Download or read book Isolation of a Breast Cancer Tumor Suppressor Gene from Chromosome 3p written by and published by . This book was released on 1995 with total page 19 pages. Available in PDF, EPUB and Kindle. Book excerpt: Loss of tumor suppressor genes by genetic mechanisms represent critical molecular events in the development and progression of breast cancer. One or more of these tumor suppressor genes likely resides on the short arm of chromosome 3 (3p) and appears to be involved in nearly 50% of breast cancers. We have identified a region in 3pl4 which undergoes recurrent homozygous deletion or rearrangement in breast cancer cell lines. A set of cloned DNA molecules spanning the target region has been established and a gene search is underway. In order to develop a functional tumor suppressor test of the 3pl4 and other target regions, we have begun to modify specific YACs with the Neomycin resistance gene that will permit their selective retention in mammalian cells. The identification of this homozygous deletion region is an exciting development that has resulted in a modification of the order for our Specific Aims.

Download or read book Isolation of Breast Tumor Suppressor Genes from Chromosome 11p written by Pratima Karnik and published by . This book was released on 2001 with total page 43 pages. Available in PDF, EPUB and Kindle. Book excerpt: In published studies, we have shown that chromosome 11p15.5 exhibits loss of heterozygosity (LOH) in ^60% of breast tumors, and that there is a significant correlation between lip LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome 11p15.5 harbors a tumor/metastasis suppressor gene. An intriguing candidate gene that we have mapped to the tumor/metastasis suppressor locus on chromosome 11p15.5 is Integrin-linked Kinase (ILK). ILK is a newly identified ankyrin-repeat containing serine/threonine kinase that binds to the cytoplasmic domains of both 81 and the 83 integrins. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed in normal breast tissue but-not in metastatic breast cancer cell lines or in advanced breast cancers. Transfection of wild-type ILK into the MDA-MBA35 mammary carcinoma cells potently suppressed their growth and invasiveness in vitro, and reduced the cells' ability to induce tumors and metastasize in athymic mice. Conversely, expression of the ankyrin repeat or catalytic domain mutants of ILK failed to suppress the growth of these cells. Growth suppression by ILK is not due to apoptosis but is mediated by its ability to block cell cycle progression in the G1 phase. These findings directly demonstrate that ILK deficiency facilitates neoplastic growth and suggest a novel role for the ILK gene in tumor suppression.

Download or read book Isolation of Breast Tumor Suppressor Genes from Chromosome Lip written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: We have previously shown that chromosome lip 15.5 exhibits loss of heterozygosity (LOH) in 60% of breast tumors, and that there is a significant correlation between lip LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome lip 15.5 harbors a metastasis suppressor gene. An intriguing candidate gene that we have mapped to the metastasis suppressor locus on chromosome lip15.5 is integrin-linked kinase (ILK). ILK is a newly identified ankyrin-repeat containing serine/threonine kinase that binds to the cytoplasmic domains of both Beta 1 and the Beta 3 integrins. Cell-cell and cell-matrix interactions are important prerequisites of the metastatic process and appear to be modulated by cell adhesion receptors called integrins. There is a growing body of evidence suggesting that variations in the expression of these molecules can have a profound effect on tumor biology. In preliminary experiments, we have provided evidence that Integrin-linked kinase expression is down-regulated in primary breast tumors and in cell lines derived from metastatic breast tumors. We have shown that ILK overexpression inhibits the growth of the highly metastatic breast cancer cell line MDA-MB-435. In addition, ILK overexpression stimulates the levels of the growth suppressing integrin alpha5Beta1 and inhibits the levels of alphavBeta3, a growth promoting integrin. These studies suggest that ILK is a breast cancer metastasis suppressor gene.

Download or read book Isolation of Genes from Chromosome Region Ip31 Involved in the Development of Breast Cancer written by and published by . This book was released on 2001 with total page 5 pages. Available in PDF, EPUB and Kindle. Book excerpt: The p31 region of chromosome 1 shows frequent (50%) loss of heterozygosity (LOH) in breast tumors. This observation implies the presence of a tumor suppressor gene in this region which, when mutated contributes to tumorigenesis. The maximal common region undergoing LOH extends over approximately 2Mbp. We have constructed a map of overlapping BAC clones spanning this region with only 4 gaps. The total available sequence from this region suggests that approximately 50-60% of it is now completed. Using gene analysis tools, we have been able to demonstrate that few full-length genes are located in this region and that the ESTs from the databases are clustered to a proximal position of the contig. The high level of sequencing completed from this region means that it will soon be possible to establish a baseline transcription map. The genes identified in this way can now be tested systematically for mutations in breast tumors. The progesterone receptor gene lies at the limit of the region suggesting that it was possibly the target for LOH. We established the exon/intron structure of this gene and undertook SSCP analysis of breast tumors. No gene-inactivating mutations were found excluding this gene from involvement in breast cancer development.

Download or read book Obzor raboty gorodskich bibliotek written by and published by . This book was released on 1967 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Mammography and Beyond written by National Research Council and published by National Academies Press. This book was released on 2001-07-23 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: Each year more than 180,000 new cases of breast cancer are diagnosed in women in the U.S. If cancer is detected when small and local, treatment options are less dangerous, intrusive, and costly-and more likely to lead to a cure. Yet those simple facts belie the complexity of developing and disseminating acceptable techniques for breast cancer diagnosis. Even the most exciting new technologies remain clouded with uncertainty. Mammography and Beyond provides a comprehensive and up-to-date perspective on the state of breast cancer screening and diagnosis and recommends steps for developing the most reliable breast cancer detection methods possible. This book reviews the dramatic expansion of breast cancer awareness and screening, examining the capabilities and limitations of current and emerging technologies for breast cancer detection and their effectiveness at actually reducing deaths. The committee discusses issues including national policy toward breast cancer detection, roles of public and private agencies, problems in determining the success of a technique, availability of detection methods to specific populations of women, women's experience during the detection process, cost-benefit analyses, and more. Examining current practices and specifying research and other needs, Mammography and Beyond will be an indispensable resource to policy makers, public health officials, medical practitioners, researchers, women's health advocates, and concerned women and their families.

Download or read book Isolation of Genes from Chronosome Region 1p31 Involved in the Development of Breast Cancer written by and published by . This book was released on 2003 with total page 34 pages. Available in PDF, EPUB and Kindle. Book excerpt: Loss of heterozygosity in the 1p3l region is a common event in breast cancer development suggesting the location of a tumor suppressor gene. Using a combination of molecular cloning and bioinformatics strategies, we identified 18 known genes and 16 predicted genes within the critical region of 1p31. Molecular analysis of selected genes such as TTC4 and the progesterone receptor (PTGFR) did not identify nonsense mutations in breast tumors. A comparison of expression profiles for the 18 known genes between tumor and normal tissue demonstrated seven which wee down regulated in breast cancer. No nonsense mutations were found in these genes although protein altering missense mutations were detected specifically in tumor DNA compared with the paired normal tissue. Verification of the rolf of any of these genes in breast cancer will require functional assays. During the course of these analyses, we also identified the CLCA2 gene in 1p31 which was down regulated in 50% of breast cancer and cell lines. Bisulfite secuencing showed that promoter methylation was the cause of the inactivation of this gene and treatment with 5-azacytidine could reactive it in the MDA-NB435 and MDA-MB231 cell lines. These results strongly suggest that CLCA2 could be a critical gene in 1p31 for breast cancer development.

Download or read book A Breast Tumor Suppressor Gene on 8p22 Identification by the Genetic Suppressor Element Approach written by and published by . This book was released on 2002 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: We are currently investigating a putative tumor suppressor gene (TSG) located at chromosomal band 8p22 and its potential gene targets that are involved in breast cancer. We previously proposed to apply the genetic suppressor element (GSE) approach to the identification of this TSG. Briefly, a library of short gene fragments will be introduced into a cell line which demonstrates suppression of clonogenicity in soft agar with the transfer of chromosome 8. Presumably, the 8p22 TSG is responsible for the suppression of clonogenicity, and the introduction of an "active" GSE from the library into the suppressed cells should inhibit the 8p22 TSG contained in the hybrid cells and allow reversion back to the parental phenotype, the ability to grow in soft agar. Any clones that form will be isolated and further evaluated, as a candidate for the TSG.

Download or read book Isolation of Breast Tumor Supressor Genes from Chronosome 11p written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: We have previously shown that chromosome 11p15.5 exhibits loss of heterozygosity (LOH) in 60% of breast tumors, and that there is a significant correlation between 11p LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome 11p15.5 harbors a metastasis suppressor gene. An intriguing candidate gene that we have mapped to the metastasis suppressor locus on chromosome 11p15.5 is Integrin-linked kinase (ILK). ILK is a newly identified ankyrin-repeat containing serine/threonine kinase that binds to the cytoplasmic domains of both 131 and the 133 integrins.

Download or read book Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15 5 written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The BRCAl gene is mutated in approximately 40% of the breast cancers seen in hereditary breast cancer. The function of the BRCAl gene is yet to be determined; however, it is thought to play a role in transcription regulation and/or DNA repair. The BE2 gene product was isolated because it was found to bind the BRCA1 protein. The BE2 gene has been localized to lip15.5, loss of heterozygosity at this locus is seen in approximately 30% of spontaneous breast cancer. It is my content that BE2 is a novel tumor suppressor gene. Functional assays are underway, which will determine if the BE2 cDNA suppresses in vitro and in vivo growth in breast cancer cell lines. The BE2 gene has been sequenced and Dr. Davis will use the sequence information to search for mutations in other breast cancer tissue. Dr. Davis will also characterize the BE2 gene product by assaying gene expression during different phases of the cell cycle. Immunohistochemistry will be used to determine the intra-cellular location of the BE2 gene product. The identification of genetic markers that have prognostic significance is quite important. BE2 may prognostic significance. This information has the potential to augment medical therapy for breast cancer.

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13 3 Assessment of Their Roles in Breast and Ovarian Carcinogenesis written by and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is one of the most common malignancies affecting women in the US. Despite the magnitude of this disease little is known about the molecular events that occur during its development. We have identified a region of less than 30 kbp, on chromosome l7pl3.3 by allelic loss mapping, which is altered in>50% of the breast tumors analyzed. Using positional cloning techniques we have identified a gene, OVCA2, within this region, which we believe may be a tumor suppressor gene.

Download or read book Use of Genetic Suppressor Elements to Identify Potential Breast Tumor Suppressor Genes written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: ING1 is recently isolated breast cancer candidate tumor suppressor gene. In this study, structure and expression of the mouse ing1 gene were analyzed. Ing1 is transcribed from three differently regulated promoters. Each of the resulting transcripts represents two exons; they share a long common region encoded by a common exon and differ in their 5'-exon sequences encoded by alternative 5'-exons. Three alternative transcripts of ing1 encode two proteins one of which is a truncated version of the other. Protein sequences encoded by mouse and human ing1 are highly conserved. Expression of ing1 mRNA expression correlates with cell proliferation suggesting a connection between cell growth regulation and ing1 expression. Embryonic stem cells with heterozygous deletion of ing1 common exon are prepared as a first step in the generation of ing1 knockout mice. Analysis of ing1 knockout animals should give important information about the role ing1 might have in carcinogenesis.

Download or read book Identification of Novel Tumor Suppressor Genes for Breast Cancer written by and published by . This book was released on 2006 with total page 43 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromosomal deletions are very common events in breast cancer. However, no TSGs have been identified from most of recurrent deletions and few identified TSGs do not account for the risk of majority of breast cancer. In additional to the classical TSGs, there are haplo-insufficient TSGs which defy the identification through mutation analysis and may be quite common. By using a new system to generate random chromosomal deletions, we identified a ~3Mbp deletion in mouse chromosome 3, which was associated with tumorigenesis. The expression of Fat4 in the deleted region was inactivated due to promoter methylation in the second allele of Fat4, and the re-expression of Fat4 suppressed the tumorigenecity, suggesting Fat4 as a strong candidate for breast tumor suppressor genes. We also found that Fat4 expression was lost in a high proportion of human breast cancers, some of which were attributed to Fat4 promoter methylation.

Download or read book Identification of Chromosome 18q Transcripts Lost in Breast Cancer written by and published by . This book was released on 2009 with total page 7 pages. Available in PDF, EPUB and Kindle. Book excerpt: A novel recurrent homozygous region of loss at 18q22.3 was detected in 50% of breast tumors by array comparative genomic hybridization. Since chromosomal regions exhibiting homozygous deletion are rare and are usually the site of tumor suppressor genes, the following hypothesis was proposed: Encoded within the region of homozygous deletion at 18q22.3 is a transcript whose loss plays a role in the development or progression of breast cancer. A custom oligonucleotide expression microarray covering the deleted region was designed and synthesized. RNA was isolated from primary human mammary epithelial cells (HMEC; Lonza), converted to fluorescently-labeled complementary RNA and hybridized to the microarray. An approximately 500 basepair sequence was found to be transcribed in breast epithelial cells. This is a novel transcript that has not been described previously. We confirmed this transcript with a quantitative PCR assay using normal breast epithelial cell cDNA. We also detected this transcript in brain, cervix, spleen and thymus tissues. To identify the full-length transcript, a brain cDNA library was screened.

Download or read book Identification of Tumor Suppressor Genes in Breast Cancer by International Mutagenesis and Functional Inactivation written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the most common malignancy in Western women, affecting up to one in 10 women during their lifetime and approximately 40,000 women dying from the disease each year in the U.S. Tumor genetic profiling through such methods as loss of heterozygosity (LOM) screening, comparative genomic hybridization (CGll), and cDNA microarrays all point to the same conclusion that a number of genetic changes are responsible for the malignant phenotype. For example, genes involved in breast cancer progression include amplification of oncogenes such as MYC, ERBB2, CCNDl and mutation of tumor suppressor genes TP53 and CHDlL. In case of hereditary breast cancer, germline mutations of tumor suppressor genes PTEN on chromosome 10q23.3, ATM on chromosome 1 lq22-q23, BRCAl on chromosome l7q21, and BRCA2 on chromosome l3ql2.3 were also shown to involve in the tumor progression 2. These data represent a significant advance in our understanding of molecular genetics of breast cancer. However, breast cancer is a heterogeneous disease that entails complex genetic alterations in which tumor suppressor genes, oncogenes, and modulator genes were mutated. Multi step genetic alterations transform normal mammary epithelial cells via the steps of hypeiplasia, premalignant change, in situ carcinoma, invasion, and metastases. Genome-wide searching for the alterations and the elucidation of molecular events involved in these steps is the main focus for new strategies targeted at diagnosis, prevention and treatment.

Download or read book Growth Suppressors of Breast Cancer Cells written by and published by . This book was released on 2000 with total page 43 pages. Available in PDF, EPUB and Kindle. Book excerpt: A genetic system has been established for the isolation of candidate tumor suppressor genes in MCF7 breast cancer cells. This system includes the IPTG-inducible episomal vector, which combines the advantages of inducible expression systems and extra-chromosomal replication systems. A cDNA library from normal human breast epithelial cells was constructed in the pEpiLac vector system, and transfected into a cell line (LAP 5) derived from the human breast cancer MCF7 cells which allows the inducible expression of the library DNA. After several rounds of selections of 6,000 independent cDNA clones, 12 sequences that confer growth inhibitory effects on LAPS cells were isolated. Sequence analysis revealed that some of these sequences are fragments of known genes, while others represent novel gene sequences with no known functions. One growth inhibitory cDNA analyzed revealed a novel gene, bop1, which encodes a previously unknown nucleolar protein that is involved in the processing of the 28S and 5.8S rRNA and in the biogenesis of the 60S ribosome. Further analysis of bop1 may lead understanding the cross-talk mechanism between rRNA processing and cell cycle progression.