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

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

Prostate cancer is the most common malignancy among men in Western industrialized countries. The molecular pathogenesis of the disease is poorly known. Over the past 10 years, chromosomal aberrations in prostate cancer have been studied with several techniques, such as loss of heterozygosity (LOH), classical cytogenetics, and molecular cytogenetics, namely with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). These analyses, especially those performed by CGH, have enabled the distinction of the predominant chromosomal regions of involvement in prostate cancer. Studies have shown that the most common chromosomal alterations in prostate cancer are losses at 1p, 6q, 8p, 10q, 13q, 16q, and 18q and gains at 1q, 2p, 7, 8q, 18q, and Xq. Fluorescence in situ hybridization (FISH) has been used to identify the target genes for some of these chromosomal alterations. For example, amplifications of AR (at Xq12), MYC (8q24), and EIF3S3 (8q23) have been found in a large fraction of hormone-refractory prostate cancer by FISH. However, many of the critical oncogenes and tumor suppressor genes located in the altered chromosomal regions have not yet been identified.
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PMID:Molecular cytogenetics of prostate cancer. 1107 16

Gain of the long arm of chromosome 8 (8q) is one of the most common gains found in the advanced prostate cancer by comparative genomic hybridization. We have previously identified a putative target gene for the 8q gain, EIF3S3, that encodes a p40 subunit of eukaryotic translation initiation factor 3 (eIF3). Here, we studied the frequency of the EIF3S3 amplification in different stages of prostate cancer and co-amplification of EIF3S3 and oncogene MYC. In addition, prognostic utility of the EIF3S3 copy number alteration was evaluated. The analyses were done with fluorescence in situ hybridization and tissue microarray technology. High-level amplification of EIF3S3 was found in 11 of 125 (9%) of pT1/pT2 tumors, 12 of 44 (27%) of pT3/pT4 tumors, and 8 of 37 (22%) of lymph node metastases as well as in 26 of 78 (33%) and 15 of 30 (50%) of hormone refractory locally recurrent tumors and metastases, respectively. The amplification was associated with high Gleason score (P < 0.001). One of the 79 tumors with EIF3S3 amplification had only two copies of MYC, whereas all tumors with amplification of MYC had also amplification of EIF3S3 indicating common co-amplification of the genes. Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas (P = 0.023). In the analyses of prostatectomy-treated patients, the amplification was not statistically significantly associated with progression-free time. In conclusion, amplification of EIF3S3 gene is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease.
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PMID:Amplification of EIF3S3 gene is associated with advanced stage in prostate cancer. 1173 59

The long arm of chromosome 8 is one of the most common regions of amplification in cancers of several organs, especially carcinomas of the breast and prostate. TRPS1, MYC and EIF3S3 genes are located in one of the minimal regions of amplification, 8q23-q24, and have been suggested to be the target genes of the amplification. Here, our goal was to study copy number and expression of the three genes in order to investigate the significance of the genes in breast and prostate cancer. By using fluorescence in situ hybridisation (FISH), we first found that TRPS1 and EIF3S3 were amplified together in about one-third of hormone-refractory prostate carcinomas. Next, we analysed the mRNA expression of the three genes by real-time quantitative RT-PCR and the gene copy number by FISH in six breast and five prostate cancer cell lines. Breast cancer cell line, SK-Br-3, which contained the highest copy number of all three genes, showed overexpression of only EIF3S3. Finally, the expression levels of TRPS1, EIF3S3 and MYC were measured in freshly frozen clinical samples of benign prostate hyperplasia (BPH), as well as untreated and hormone-refractory prostate carcinoma. The TRPS1 and MYC expression levels were similar in all prostate tumour groups, whereas EIF3S3 expression was higher (P=0.029) in prostate carcinomas compared to BPH. The data suggest that the expression of EIF3S3 is increased in prostate cancer, and that one of the mechanisms underlying the overexpression is the amplification of the gene.
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PMID:Expression and copy number analysis of TRPS1, EIF3S3 and MYC genes in breast and prostate cancer. 1499 5

Prostate cancer incidence is steadily increasing in Western industrialized countries where it has become the most common male malignancy and second most common cause of cancer death among men. Despite efforts to understand the mechanisms of prostate cancer development and progression, the reasons for the disease remain unclear. Although recurrent DNA copy number aberrations in prostate cancer have been well documented in the past 15 years, most of the target genes for these aberrations remain to be identified. The most common DNA copy number aberrations are losses in chromosomes 5q, 6q, 8p, 10q, 13q, 16q, 17p, and 18q, and gains in 7p/q, 8q, 9p, and Xq. In addition, a chromosomal rearrangement in 21q has been observed in over 50% of prostate cancers. The target genes for two common chromosomal aberrations have been identified: the androgen receptor (AR) gene at Xq12, and TMPRSS2 and ERG at 21q. Putative target genes for other copy number aberrations include: NKX3-1 (8p loss), PTEN and MXI1 (10q loss), FOXO1A (13q loss), CDH1 and ATBF1 (16q loss), MCM7 and EZH2 (7q gain), TCEB1, EIF3S3 and MYC (8q gain). The identification of target genes for the chromosomal aberrations will provide new prognostic markers and therapeutic targets for future drug development.
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PMID:Chromosomal aberrations in prostate cancer. 1748 99

Amplification of the long arm of chromosome 8 is one of the most recurrent findings in prostate cancer and it is associated with poor prognosis. Several minimal regions of amplification suggest multiple target genes which are yet to be identified. We have previously shown that TCEB1, EIF3S3, KIAA0196 and RAD21 are amplified and overexpressed in prostate cancer and they are located in the 8q area. In this study, we examined the functional effects of these genes to prostate cancer cell phenotype. We overexpressed and inhibited the genes by lentivirus mediated overexpression and RNA interference, respectively. shRNA mediated TCEB1 silencing decreased significantly cellular invasion of PC-3 and DU145 cells through Matrigel. TCEB1 silencing reduced the anchorage-independent growth of PC-3 cells. Similar effects were not seen with any other genes. When overexpressed in NIH 3T3 cells, TCEB1 and EIF3S3 increased the growth rate of the cells. Transcriptional profiling of TCEB1 silenced PC-3 cells revealed decrease of genes involved in invasion and metastasis. Finally, we also confirmed here the overexpression of TCEB1 in hormone-refractory prostate tumors. This study indicates that TCEB1 promotes invasion of prostate cancer cells, is involved in development of hormone-refractory prostate cancer and is thereby a strong candidate to be one of the target genes for the 8q gain.
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PMID:TCEB1 promotes invasion of prostate cancer cells. 1884 14