This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carter, B. S. Articles by Isaacs, W. B. Search for Related Content PubMed PubMed Citation Articles by Carter, B. S. Articles by Isaacs, W. B.

ras Gene Mutations in Human Prostate Cancer¹

Brady Urological Research Institute [B. S. C., W. B. I.] and Department of Pathology [J. I. E.], The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland 21205

Point mutations at codons 12, 13, or 61 of the Ha-, Ki-, and N-ras genes are able to convert these normal cellular genes into activated oncogenes. Previous studies have shown that ras gene mutations occur in a variety of human solid tumors and may be important in the pathogenesis of some of these tumors. In order to test the hypothesis that ras gene mutations may be associated with prostate cancer, we have used an oligodeoxynucleotide hybridization assay to detect wild-type and mutant alleles in genomic DNA from prostate tumors and prostate tumor cell lines amplified using the polymerase chain reaction. Twenty-four primary prostate tumors (23 acinar tumors and one ductal tumor) and five prostate tumor cell lines were examined for mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes. Two mutations were detected: an A G transition causing a glutamine to arginine amino acid substitution at codon 61 of the Ha-ras gene in a primary prostatic duct adenocarcinoma and a G T transversion causing a glycine to valine amino acid substitution at codon 12 of the Ha-ras gene in a prostate tumor cell line (TSU-PR1) derived from a lymph node metastasis. While the overall frequency of ras gene mutations in prostate tumors is low, when these mutations do occur they may have a role in the progression of disease or the development of the unusual ductal variant of prostatic adenocarcinoma.

¹ This work was supported in part by NIH Grant CA09314 and the Edwin Beer Program, New York Academy of Medicine.

² To whom reprint requests should be addressed, at James Buchanan Brady Urological Institute Research Laboratories, The Johns Hopkins Hospital, Baltimore, MD 21205.

Received 4/30/90. Accepted 7/13/90.

This article has been cited by other articles:

				K. Bray, H.-Y. Chen, C. M. Karp, M. May, S. Ganesan, V. Karantza-Wadsworth, R. S. DiPaola, and E. White Bcl-2 Modulation to Activate Apoptosis in Prostate Cancer Mol. Cancer Res., September 1, 2009; 7(9): 1487 - 1496. [Abstract] [Full Text] [PDF]

				J. Zhoul, G. Hernandez, S.-W. Tu, C.-L. Huang, C.-P. Tseng, and J.-T. Hsieh The Role of DOC-2/DAB2 in Modulating Androgen Receptor-Mediated Cell Growth via the Nongenomic c-Src-Mediated Pathway in Normal Prostatic Epithelium and Cancer Cancer Res., November 1, 2005; 65(21): 9906 - 9913. [Abstract] [Full Text] [PDF]

				M. Stearns, J. Tran, M. K. Francis, H. Zhang, and C. Sell Activated Ras Enhances Insulin-Like Growth Factor I Induction of Vascular Endothelial Growth Factor in Prostate Epithelial Cells Cancer Res., March 15, 2005; 65(6): 2085 - 2088. [Abstract] [Full Text] [PDF]

				M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]

				R. Foley, D. Hollywood, and M. Lawler Molecular pathology of prostate cancer: the key to identifying new biomarkers of disease Endocr. Relat. Cancer, September 1, 2004; 11(3): 477 - 488. [Abstract] [Full Text] [PDF]

				J. R. Brody, S. S. Kadkol, M. C. Hauer, F. Rajaii, J. Lee, and G. R. Pasternack pp32 Reduction Induces Differentiation of TSU-Pr1 Cells Am. J. Pathol., January 1, 2004; 164(1): 273 - 283. [Abstract] [Full Text] [PDF]

				R. E. Bakin, D. Gioeli, R. A. Sikes, E. A. Bissonette, and M. J. Weber Constitutive Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway Promotes Androgen Hypersensitivity in LNCaP Prostate Cancer Cells Cancer Res., April 15, 2003; 63(8): 1981 - 1989. [Abstract] [Full Text] [PDF]

				G. Narla, S. L. Friedman, and J. A. Martignetti Kruppel Cripples Prostate Cancer: KLF6 Progress and Prospects Am. J. Pathol., April 1, 2003; 162(4): 1047 - 1052. [Full Text] [PDF]

				S. Goodin, K. V. Rao, and R. S. DiPaola State-of-the-Art Treatment of Metastatic Hormone-Refractory Prostate Cancer Oncologist, August 1, 2002; 7(4): 360 - 370. [Abstract] [Full Text] [PDF]

				M. Chakraborty, S. G. Qiu, K. M. Vasudevan, and V. M. Rangnekar Par-4 Drives Trafficking and Activation of Fas and FasL to Induce Prostate Cancer Cell Apoptosis and Tumor Regression Cancer Res., October 1, 2001; 61(19): 7255 - 7263. [Abstract] [Full Text] [PDF]

				A. F. Fribourg, K. E. Knudsen, M. W. Strobeck, C. M. Lindhorst, and E. S. Knudsen Differential Requirements for Ras and the Retinoblastoma Tumor Suppressor Protein in the Androgen Dependence of Prostatic Adenocarcinoma Cells Cell Growth Differ., July 1, 2000; 11(7): 361 - 372. [Abstract] [Full Text]

				B.-J. Park, J.-I. Park, D.-S. Byun, J.-H. Park, and S.-G. Chi Mitogenic Conversion of Transforming Growth Factor-{beta}1 Effect by Oncogenic Ha-Ras-induced Activation of the Mitogen-activated Protein Kinase Signaling Pathway in Human Prostate Cancer Cancer Res., June 1, 2000; 60(11): 3031 - 3038. [Abstract] [Full Text] [PDF]

				P. J Medina, R. S DiPaola, and S. Goodin Treatment of hormone-refractory prostate cancer Journal of Oncology Pharmacy Practice, March 1, 1999; 5(1): 32 - 48. [Abstract] [PDF]

				E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken Molecular Genetics and Epidemiology of Prostate Carcinoma Endocr. Rev., February 1, 1999; 20(1): 22 - 45. [Abstract] [Full Text]

				M. Zhang, D. Magit, and R. Sager Expression of maspin in prostate cells is regulated by a positive Ets element and a negative hormonal responsive element site recognized by androgen receptor PNAS, May 27, 1997; 94(11): 5673 - 5678. [Abstract] [Full Text] [PDF]

				W.B. Isaacs, G.S. Bova, R.A. Morton, M.J.G. Bussemakers, J.D. Brooks, and C.M. Ewing Genetic Alterations in Prostate Cancer Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 653 - 659. [Abstract] [PDF]