Clinical Cancer Research, Vol 1, Issue 12 1471-1478, Copyright © 1995 by American Association for Cancer Research

ARTICLES

Regional loss of imprinting of the insulin-like growth factor II gene occurs in human prostate tissues

DF Jarrard, MJ Bussemakers, GS Bova and WB Isaacs
Brady Urological Institute, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.

In most tissues, the insulin-like growth factor II gene (IGF-II) demonstrates imprinting, being expressed exclusively from the paternal allele. Recently, a loss of IGF-II imprinting (i.e., biallelic expression) has been found in sporadic Wilm's tumors and lung carcinomas, and this molecular event may contribute to the pathogenesis of these tumors. Here, we report that in prostates removed at radical surgery for localized adenocarcinoma, both the cancer and the associated normal peripheral zone tissue have a pronounced biallelic expression of the IGF-II gene. However, this pattern of gene expression is uncommon in periurethral samples of benign prostatic hyperplasia (BPH) from the same specimens. 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 synthesis and subsequent PCR amplification were performed on 13 of 35 radical prostatectomy specimens found to be informative for analysis of allele-specific expression. Biallelic expression for IGF-II RNA was demonstrated in 10 (83%) of 12 tumor samples and 8 (73%) of 11 matched peripheral zone prostate samples but in only 2 (18%) of 11 BPH samples. RNA transcripts were readily demonstrated by Northern blot analysis, and differences in expression were not noted among normal, BPH, and tumor prostate tissues. In situ hybridization revealed production of IGF-II by both the epithelium and stroma. The finding of a frequent biallelic expression of IGF-II in peripheral prostate specimens suggests a regional pattern of IGF-II gene regulation exists in prostate tissue. We hypothesize that this tissue-specific pattern of gene expression may participate in the marked predilection of peripheral prostatic tissue for the development of carcinogenesis.

This article has been cited by other articles:

				V. X. Fu, J. R. Dobosy, J. A. Desotelle, N. Almassi, J. A. Ewald, R. Srinivasan, M. Berres, J. Svaren, R. Weindruch, and D. F. Jarrard Aging and Cancer-Related Loss of Insulin-like Growth Factor 2 Imprinting in the Mouse and Human Prostate Cancer Res., August 15, 2008; 68(16): 6797 - 6802. [Abstract] [Full Text] [PDF]

				A. S Perry, R. Foley, K. Woodson, and M. Lawler The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 357 - 377. [Abstract] [Full Text] [PDF]

				S. K. Murphy, Z. Huang, Y. Wen, M. A. Spillman, R. S. Whitaker, L. R. Simel, T. D. Nichols, J. R. Marks, and A. Berchuck Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer Mol. Cancer Res., April 1, 2006; 4(4): 283 - 292. [Abstract] [Full Text] [PDF]

				V. X. Fu, S. R. Schwarze, M. L. Kenowski, S. LeBlanc, J. Svaren, and D. F. Jarrard A Loss of Insulin-like Growth Factor-2 Imprinting Is Modulated by CCCTC-binding Factor Down-regulation at Senescence in Human Epithelial Cells J. Biol. Chem., December 10, 2004; 279(50): 52218 - 52226. [Abstract] [Full Text] [PDF]

				B. S. Schaffer, M.-F. Lin, J. C. Byrd, J. H. Y. Park, and R. G. MacDonald Opposing Roles for the Insulin-Like Growth Factor (IGF)-II and Mannose 6-Phosphate (Man-6-P) Binding Activities of the IGF-II/Man-6-P Receptor in the Growth of Prostate Cancer Cells Endocrinology, March 1, 2003; 144(3): 955 - 966. [Abstract] [Full Text] [PDF]

				J. D. Ravenel, K. W. Broman, E. J. Perlman, E. L. Niemitz, T. M. Jayawardena, D. W. Bell, D. A. Haber, H. Uejima, and A. P. Feinberg Loss of Imprinting of Insulin-Like Growth Factor-II (IGF2) Gene in Distinguishing Specific Biologic Subtypes of Wilms Tumor J Natl Cancer Inst, November 21, 2001; 93(22): 1698 - 1703. [Abstract] [Full Text] [PDF]

				A. T. Weeraratna, S. L. Dalrymple, J. C. Lamb, S. R. Denmeade, S. Miknyoczki, C. A. Dionne, and J. T. Isaacs Pan-trk Inhibition Decreases Metastasis and Enhances Host Survival in Experimental Models as a Result of Its Selective Induction of Apoptosis of Prostate Cancer Cells Clin. Cancer Res., August 1, 2001; 7(8): 2237 - 2245. [Abstract] [Full Text] [PDF]

				H. Yu and T. Rohan Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression J Natl Cancer Inst, September 20, 2000; 92(18): 1472 - 1489. [Abstract] [Full Text] [PDF]

				J. G. Falls, D. J. Pulford, A. A. Wylie, and R. L. Jirtle Genomic Imprinting: Implications for Human Disease Am. J. Pathol., March 1, 1999; 154(3): 635 - 647. [Abstract] [Full Text] [PDF]

				J. Svaren, T. Ehrig, S. A. Abdulkadir, M. U. Ehrengruber, M. A. Watson, and J. Milbrandt EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis J. Biol. Chem., December 1, 2000; 275(49): 38524 - 38531. [Abstract] [Full Text] [PDF]