REGIONAL LOSS OF IMPRINTING OF THE INSULIN-LIKE GROWTH-FACTOR-II GENEOCCURS IN HUMAN PROSTATE TISSUES

In most tissues, the insulin-like growth factor II gene (IGF-II) demon strates imprinting, being expressed exclusively from the paternal alle le, Recently, a loss of IGF-II imprinting (i.e., biallelic expression) has been found in sporadic Wilm's tumors and lung carcinomas, and thi s molecular event may contribute to the pathogenesis of these tumors, Here, we report that in prostates removed at radical surgery for local ized adenocarcinoma, both the cancer and the associated normal periphe ral zone tissue have a pronounced biallelic expression of the IGF-II g ene, However, this pattern of gene expression is uncommon in periureth ral samples of benign prostatic hyperplasia (BPH) from the same specim ens, We analyzed the status of genomic imprinting at the IGF-II locus in prostate specimens removed for carcinoma using an ApaI polymorphism in the 3' untranslated exon of the IGF-II gene, First-strand cDNA syn thesis and subsequent PCR amplification were performed on 13 of 35 rad ical prostatectomy specimens found to be informative for analysis of a llele-specific expression, Biallelic expression for IGF-II RNA was dem onstrated in 10 (83%) of 12 tumor samples and 8 (73%) of 11 matched pe ripheral zone prostate samples but in only 2 (18%) of 11 BPH samples, RNA transcripts were readily demonstrated by Northern blot analysis, a nd differences in expression were not noted among normal, BPH, and tum or prostate tissues, In situ hybridization revealed production of IGF- II by both the epithelium and stroma, The finding of a frequent bialle lic expression of IGF-II in peripheral prostate specimens suggests a r egional pattern of IGF-II gene regulation exists in prostate tissue, W e hypothesize that this tissue-specific pattern of gene expression may participate in the marked predilection of peripheral prostatic tissue for the development of carcinogenesis.