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 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 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 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 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 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 Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11P15 5 written by and published by . This book was released on 1997 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: Loss of heterozygosity (LOH) on the short arm of chromosome 11 has been demonstrated in many cancers, suggesting the presence of a tumor suppressor gene. A number of studies have narrowed the region showing LOH in breast tumors to l1p15.5. The objectives of this study are: to screen breast tumor samples for LOH to further resolve the location of the putative tumor suppressor gene: and to screen candidate genes from this region. We are examining LOH in our region of interest using polymorphic markers. Samples from heterozygous individuals are examined from both normal and tumor tissue. We have isolated genomic DNA from 112 tissue samples, constituting 56 matched tumor and normal pairs. These samples are being analyzed for loss of heterozygosity (LOH) at three separate polymorphic markers, D11S1318, D11S4088, and D11S860. The analysis of marker D11S1318 is complete and is comparable to results which have been previously been reported at 6 percent LOH. To date D11S4088 is showing 12 percent LOH and D11S860 is incomplete.
Download or read book Tumor Suppressor Genes written by George Klein and published by Marcel Dekker. This book was released on 1990 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: These dozen articles treat a category of genes described as antioncogenes, tumor suppressor genes, or emerogenes, which can antagonize tumorigenic behavior at various levels. The four mechanisms or processes of tumor suppression discussed are the somatic hybridization of normal and malignant cells, physiological or chemical differentiation that down-regulates oncoprotein expression, the overriding of oncogenes by cellular genes as revertants, and the loss or mutational inactivation of "recessive cancer genes". Annotation(c) 2003 Book News, Inc., Portland, OR (booknews.com)
Download or read book Identification and Characterization of Molecular Abnormalities of 11p Genes in Human Breast Cancer written by and published by . This book was released on 1996 with total page 25 pages. Available in PDF, EPUB and Kindle. Book excerpt: This project is based on the hypothesis that at least one tumor suppressor gene on chromosomal band 11p15 is involved in breast cancer progression. This hypothesis is based on the fact that loss of heterozygosity (LOH) of 11pl5 occurs in at least half of breast cancers that metastasize, and that a normal chromosome 11 suppresses tumorigenicity of MCF-7 breast cancer cells. The purpose of these studies is to localize and identify an 11p15 breast cancer gene.
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 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 Identification of Tumor Suppressor Genes in Breast Cancer by Insertional Mutagenesis and Functional Inactivation written by YAN. SU and published by . This book was released on 1998 with total page 19 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development and progression of cancer result from multiple genetic changes accumulated in the cells. The identification of tumor suppressor genes inactivated and proto-oncogenes activated in mammary epithelial cells is essential to understand the genetic basis of breast cancer and is a prerequisite for development of strategies for prevention, diagnosis, and treatment. In breast cancer, loss of heterozygosity (LOH) was detected frequently on chromosome 17 and other chromosomes, suggesting unrecognized tumor suppressor genes. We are applying the novel retroviral-tagging strategy to identify the genes using chromosome 17-suppressed (independent of p53 and BRCAl) breast cancer cell lines. In contrast to the parental tumorigenic cell line CAL51, the suppressed sublines CAL/17-3 and CAL/17-5 display retard growth in flasks, no growth in soft-agar culture and athymic nude mice. In this annual report, we present preparation of biological materials including cell culture, isolation of DNA and RNA, construction of cDNA library and packaging retrovirus particles. In order to provide antisense and mutant proteins to inhibit activities of tumor suppressor genes, poly-(A)+RNA was isolated from the suppressed subline CAL17-3 and used to construct the library. We are now in the process to package cDNA library into retrovirus particles for transduction.
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 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 Characterization of Putative Proto Oncogenes and Tumor Suppressor Genes That Are Transcriptionally Deregulated in Breast Cancer written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Candidate proto-oncogenes and tumor suppressor genes were previously isolated in a gene expression study involving breast cancer. The present research focus on the characterization of genetic alterations associated with presenilin-2 (PS-2), a gene identified in the gene expression a%alysis. PS-2 has been implicated in the pathogenesis of Alzheimer's disease, but functional studies indicate that the gene plays a role in pathways commonly perturbed in cancer, hence suggesting that PS-2 may be a target for genetic alterations in tumors. PS-2 maps to a chromosomal region for which LOH/deletion in breast tumors has been reported. We found low PS-2 expression in a fraction of breast tumors. In some cases, the reduction in expression can be attributed to deletion at the PS-2 genomic locus. In addition, we identified two sequence alterations in PS-2 which resulted in amino acid substitutions. Both of the alterations were observed to affect the physiological activity of PS-2, but appear not to be contributing to the Alzheimer's phenotype. The alterations may indeed contribute to mammary tumorigenesis and we are in the process of further exploring this possibility.
Download or read book Public Documents Federal Provincial Territorial Conference of Ministers of Health Toronto Ontario September 10 11 1996 written by and published by . This book was released on 1996 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Tumor Suppressor Genes written by Wafik S. El-Deiry and published by Humana PressInc. This book was released on 2003-03-03 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leading physician scientists and academic researchers review all the known tumor suppressor genes, explain how they work, and describe how they were discovered and isolated. In many cases, the authors discuss specific genes that are frequently involved in hereditary or sporadic cancers. They also provide a detailed guide to using powerful molecular genetic, cytogenetic, proteomic, and cell biological strategies to discover and isolate novel tumor suppressor genes and their targets. For both volumes: Leading physician scientists and academic researchers review all the known tumor suppressor genes, explain how they work, and describe how they were discovered and isolated. In many cases, the authors discuss specific genes that are frequently involved in hereditary or sporadic cancers. They also provide a detailed guide to using powerful molecular genetic, cytogenetic, proteomic, and cell biological strategies to discover and isolate novel tumor suppressor genes and their targets. A second volume of this two-volume set, Tumor Suppressor Genes, Volume 2: Regulation, Function, and Medical Applications, shows how to explore the cell biology and biochemical function of such encoded proteins, to study its physiological role in vivo, and to use information on TSGs to develop diagnostic and therapeutic strategies for cancer.
