Expression mapping at 12p12‐13 in advanced prostate carcinoma

Abstract

We have previously mapped a putative prostate cancer tumor-suppressor gene to a 1-2 Mb region of 12p12-13. Initial work to identify the tumor suppressor at this locus focused on candidates previously implicated in malignancy; however, mutational and methylation analyses failed to identify significant genomic events. An alternative approach is to use expression analysis to prioritize the genes within the region of interest. This experimental design is based on the hypothesis that tumor-suppressor genes demonstrate decreased expression in tumors compared to normals. Herein, we narrow the region of interest using deletion mapping data and employ expression analysis to prioritize the genes in the minimal deleted region. Highly informative polymorphic markers spanning our region were used to assess for loss of heterozygosity in 99 tumor and normal DNA pairs. The minimal region of deletion was determined to be approximately 500 kb bounded by D12S391 and A002Q26. Publically available databases place 7 genes within this minimal deletion region. An additional 3 genes lie just outside this minimal deletion region and could possibly be inactivated by deletion of promoter, 3 -untranslated region sequences or alternative splice variants. Relative levels of expression of these 10 candidate genes were determined in 6 normal prostates, 5 local prostate tumors, 9 prostate lymph node metastases, 6 prostate cancer cell lines and 12 prostate cancer xenografts using quantitative RT-PCR. DUSP16, FLJ10298 and BCLG were significantly downregulated in both clinical tumors and cultured prostate cancer tissue, indicating that one or all may be critical to initiation or progression of prostate carcinoma.

Phosphorylation of Ser-446 Determines Stability of MKP-7

“…Recently it was reported that among 22 leukemia patients analyzed, 17 were hemizygous for MKP-7/DUSP16, but no inactivating mutations could be detected (35), and investigators hypothesized that MKP-7/DUSP16 could be haploinsufficient for tumor suppression. Another group also reported that expression of MKP-7/DUSP16 gene is significantly down-regulated in both clinical tumors and cultured prostate cancer cell lines (36). These data suggest that down-regulation of the MKP-7/DUSP16 gene may be critical for initiation or progression of several tumors.…”

FAU regulates carboplatin resistance in ovarian cancer

“…BCL-G is a proapoptotic protein (Guo et al, 2001), which has been implicated in the activation of T-cells (Nakamura and Tanigawa, 2003) and has been shown to be significantly downregulated in prostate cancer compared with normal prostate tissue (Kibel et al, 2004). FAU and BCL-G have been investigated in apoptosis activation in breast cancer where studies indicate that they act through a common pathway (Pickard et al, 2009).…”

Down-Regulation of CD9 Expression during Prostate Carcinoma Progression Is Associated with CD9 mRNA Modifications

“…Indeed, a small region of the long arm of this chromosome was sufficient to inhibit prostate cancer metastatic colonization of the Dunning AT6.1 rat prostate cancer cell line (3). Moreover, loss of heterozygosity (4) as well as reduced expression of specific genes present in a 2-Mb region of chromosome 12p12-13 has been associated with advanced prostate adenocarcinoma (5). Using irradiation, we further fragmented chromosome 12, and radiation hybrids exhibiting either tumorigenic or nontumorigenic phenotypes, depending on the portion of chromosome 12 retained, were generated.…”