Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer
Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer
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DOI：
10.1016/s0002-9440(10)65433-8
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发表时间：
1999-06-01
影响因子：
6
通讯作者：
Visakorpi, T
中科院分区：
文献类型：
--
作者：
Nupponen, NN;Porkka, K;Visakorpi, T
在大部分乳腺癌和前列腺癌中，8号染色体长臂发生扩增。为了克隆这种扩增的靶基因，我们使用抑制消减杂交来鉴定乳腺癌细胞系SK-Br-3中的过表达基因，其在8 q处具有扩增（8 q21和8 q23-q24），一个通过SSH鉴定的差异表达基因，真核生物翻译起始因子3（eIF 3）的p40亚基，定位于8 q23，并发现在研究的乳腺癌和前列腺癌细胞系中高度扩增和过表达。在30%的难治性前列腺肿瘤和18%的未经治疗的原发性乳腺肿瘤中发现了eIF 3-p40的高水平扩增。在绝大多数情况下，p40和c-myc以相等的拷贝数扩增。原位杂交检测p40 mRNA表达。eIF 3-p40基因的扩增与其mRNA的过表达相关，正如扩增的功能靶基因所预期的那样。这些结果表明，基因组畸变的翻译起始因子，如eIF 3-p40，可能有助于乳腺癌和前列腺癌的发病机制。
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.