Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 99, Issue 5, Pages 689-696Publisher
WILEY
DOI: 10.1002/ijc.10393
Keywords
CHC1-L; prostate cancer; loss of heterozygosity; 13q14 locus; real-time quantitative RT-PCR
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Loss of heterozygosity (LOH) at chromosome 13q14 is one of the most recurrent anomalies observed in sporadic prostate tumors. This LOH is believed to unmask recessive mutations that inactivate a tumor-suppressor gene(s) which otherwise regulates normal cell growth and suppresses abnormal cell proliferation. Identification of potential tumor-suppressor genes within the deleted region is a way of indicating putative pathways of prostate cancer development and progression. The main target that disappears or is down-regulated as a result of 13q14 loss remains to be identified. Therefore, our first concern was to find a gene located in the 13q14 region whose transcription is reduced. CHCI-L, for chromosome condensation I-like, is mapped to the smallest common deleted region. CHCI-L expression is significantly reduced in prostate tumors compared to normal prostate tissues (p = 0.0002). In 21 of 36 (58%) primary prostate tumors studied, CHCI-L expression was reduced at least 2-fold, as measured by real-time quantitative RT-PCR; 18 of the tumors (50%) showed 13q14 LOH for at least I of the 5 polymorphic markers that we studied in the region, and 14 (78%) of these were among the tumors underexpressing CHCI-L. CHCI-L is alternatively spliced at its 5' end to produce 2 isoforms, of 551 and 526 aa. Analyses of CHCI-L integrity and of the quantitative expression of its variants indicate that the observed underexpression in prostate tumors is related to reduced expression of the 55 1 aa isoform. Although CHCI-L is not the obvious candidate given its only known homology, to RCCI, a guanine nucleotide exchange factor for the Ras-related GTPase Ran, the frequent significant decrease observed in its expression in prostate cancer associated with the difference in frequency of CHCI-L variant isoforms between normal and neoplastic prostate tissues places it in a pivotal role or possibly adjacent to a gene tat has that role in prostate cancer evolution. (C) 2002 Wiley-Liss, Inc.
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