Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amplification at the long arm of chromosome 8 occurs in a large fraction of breast and prostate cancers. To clone the target genes for this amplification, we used suppression subtraction hybridization to identify overexpressed genes in the breast cancer cell line SK-Br-3, which harbors amplification at 8q (8q21 and 8q23-q24). A differentially expressed gene identified by SSH, the p40 subunit of eukaryotic translation initiation factor 3 (eIF3), was localized to 8q23 and found to be highly amplified and overexpressed in the breast and prostate cancer cell lines studied. High-level amplification of eIF3-p40 was found in 30% of hormone-refractory prostate tumors and in 18% of untreated primary breast tumors. In the vast majority of the cases, p40 and c-myc were amplified with equal copy numbers. Tumors with higher copy numbers of p40 than c-myc were also found. Expression of p40 mRNA was analyzed with in situ hybridization. The amplification of eIF3-p40 gene was associated with overexpression of its mRNA, as expected for a functional target gene of the amplification. These results imply that genomic aberrations of translation initiation factors, such as eIF3-p40, may contribute to the pathogenesis of breast and prostate cancer.
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PMID:Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer. 1036 2

Gain of chromosome arm 8q is a frequent genetic alteration in breast and prostate cancer. Two amplified subregions, 8q21 and 8q23-24, have been identified with comparative genomic hybridization (CGH). We have recently demonstrated that the EIF3S3 (eIF3-p40) gene, located at 8q23, is often amplified and overexpressed in both breast and prostate cancer. Here, we used fluorescence in situ hybridization (FISH) to map the amplified region around EIF3S3 in primary breast cancers and cell lines. The size of the common highly amplified region was about 2.5 Mb between the markers D8S1668 and WI-7959. Next, we analyzed the expression of all expressed sequence tags (ESTs) located within and near this region by RNA slot blot hybridization. In addition to EIF3S3, three anonymous ESTs and EXT1 were found to be highly expressed in cancer cell lines with the amplification at 8q23-q24. However, the anonymous ESTs were located outside the minimal highly amplified region and EXT1 was overexpressed only in one of the cancer cell lines with 8q amplification. Since EIF3S3 was the only consistently overexpressed gene located in the minimal highly amplified region, it is the strongest candidate target gene for 8q23-q24 amplification.
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PMID:Mapping the amplification of EIF3S3 in breast and prostate cancer. 1082 5

The molecular genetics of prostate cancer, the second most common cause of cancer-related death in men, is poorly understood. Inherited factors are believed to account for 42% of the risk of prostate cancer, and although multiple chromosomal loci of susceptibility have been identified, the target genes for these loci have not been well defined. Its heterogeneous nature suggests that the predisposition to prostate cancer may involve multiple genes and variable phenotypic expression. Genes that have been found to play a role in progression of prostate cancer include GSTP1 and PTEN, as well as the androgen receptor (AR) gene. Evidence suggests that the AR signaling pathway can be activated by other ligands when androgen levels are low. Recent findings have also implicated Kruppel-like factor 6 (KFL6), E-cadherin, the p40 subunit of eukaryotic translation initiation factor (eIF3-p40), and Elongin C, but confirmatory evidence is required to clarify the roles of these factors. Technologic advances, such as complementary DNA and tissue microarrays, have facilitated identification of genetic alterations and investigations of their function, but improved tools for searching and analyzing genes are still needed.
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PMID:The molecular genetics of prostate cancer. 1460 12