Amplification and Overexpression of p40 Subunit of Eukaryotic Translation Initiation Factor 3 in Breast and Prostate Cancer

Abstract

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.

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

“…It is noteworthy that eIF3 and CDC23, which are the homologues of eIF4 and CDC27, respectively, were identified in our screening. Some of the proteins that we identified have already been reported to be overexpressed in various types of cancer, including ribosomal protein S18 (Chassin et al, 1994), RAN binding protein 7 (Li et al, 2000), and eIF3, p40 subunit (Nupponen et al, 1999). Therefore, given the aberrant expression of these proteins in various malignancies, it is not surprising that they elicit immune responses.…”

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

“…The most significant gain comparing ductal carcinoma with lobular carcinomas mapped to 8q24.11 (117.8 -118.0 Mb), which encompasses RAD21 and eucaryotic translation initiation factor 3, subunit 3 gamma (EIF3S3). RAD21 is believed to function in sister chromatid alignment as part of the cohesin complex and also in double-strand break repair and influences cellular proliferation (Atienza et al, 2005), whereas EIF3S3 is reported to be amplified and overexpressed in up to 20% of breast carcinomas (Nupponen et al, 1999). Our observations are consistent with previous studies on breast cancer, confirming the robustness of our aCGH protocol, the validity of our analysis method and the likelihood that we have a representative set of tumours.…”

Expression and copy number analysis of TRPS1, EIF3S3 and MYC genes in breast and prostate cancer

“…For example, about 70 -90% of metastatic and/or hormone-refractory prostate carcinomas as well as about 50% of untreated breast cancers contain gain of 8q by CGH (Visakorpi et al, 1995;Cher et al, 1996;Tirkkonen et al 1998;Nupponen et al, 1999). The gain of 8q has also been found to be associated with an aggressive phenotype and poor prognosis in these malignancies Alers et al, 2000).…”

“…Two minimal regions of amplification, 8q21 and 8q23 -q24, have been identified in prostate cancer by CGH analyses (Cher et al, 1996;Nupponen et al, 1998). Several putative target genes, such as MYC, PSCA, EIF3S3 and TRPS1, have been proposed for the amplification of 8q23 -24 (Jenkins et al, 1997;Reiter et al, 1998;Nupponen et al, 1999;Chang et al, 2000;Rummukainen et al 2001). However, the significance of each of these genes in tumorigenesis is unclear.…”