Characterization of frequently deleted 6q locus in prostate cancer.

The long arm of chromosome 6 is frequently deleted in diverse human neoplasms. Our previous study showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary prostate cancer (CaP). In this study, we further refined a 200-kb minimal region of deletion (6qTSG1) centered around D6S1013 marker. The 6qTSG1 transcripts contained complex multiple splicing variants with low or absent expression in CaP cells. None of the transcripts identified contained open reading frames that code for a protein in the NCBI database. The expression of 6qTSG transcripts revealed interesting hormonal regulation relevant to CaP biology. Expression of 6q TSG transcript was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an upregulation of 6qTSG transcript by androgen ablation and cell growth inhibition/apoptosis. Induction of 6qTSG1 expression in response to androgen ablation was abrogated in androgen-independent derivatives of LNCaP cells. In summary, we have defined a candidate CaP suppressor locus on chromosome 6q16.1, and deletions of this locus are frequently associated with prostate tumorigenesis. In the light of emerging role of noncoding RNAs in cancer biology including CaP, future investigations of 6qTSG11 locus is warranted.

A human novel gene DERPC on 16q22.1 inhibits prostate tumor cell growth and its expression is decreased in prostate and renal tumors.

BACKGROUND: Deletion of chromosome 16q is frequently associated with diverse tumors. Numerous studies strongly suggest the presence of one or more tumor suppressor genes on chromosome 16q22 to 16qter including the widely studied cadherin gene family. However, the specific tumor suppressor genes residing in this region need better definition and characterization. MATERIAL AND METHODS: Standard molecular biology approaches have been used to clone and characterize the DERPC cDNA and its protein product on chromosome 16q22.1. Northern blotting was used to define the expression pattern in a multiple human tissue blots. DERPC expression was examined in multi-tumor array (Clontech, CA, USA) dot blot as well as in laser capture microdissection (LCM) derived prostate cancer (CaP) specimens by quantitative RT-PCR. Western blot analysis and a fluorescent microscopy were used to characterize the molecular size and the cellular location of green fluorescent protein (GFP)-tagged DERPC fusion proteins. A colony formation assay was conducted to determine the effects of DERPC expression on tumor cell growth. RESULTS: A novel gene DERPC (Decreased Expression in Renal and Prostate Cancer) was identified and characterized. DERPC encoded a strong basic, proline- and glycine-rich nuclear protein. DERPC was ubiquitously expressed, with abundant expression in kidney, skeletal muscle, testis, liver, ovary, and heart and moderate expression in prostate. DERPC expression was reduced in renal (67%) and prostate tumors (33%). Expression of DERPC has inhibitory potential on CaP cell growth. Further, overexpression of DERPC in LNCaP cells caused alterations of nuclear morphology. CONCLUSION: This study suggests that decreased expression of DERPC may be implicated in tumorigenesis of renal and CaPs.