This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Yasunaga, Y. Articles by Rhim, J. S. Search for Related Content PubMed PubMed Citation Articles by Yasunaga, Y. Articles by Rhim, J. S.

A Novel Human Cell Culture Model for the Study of Familial Prostate Cancer

Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 [Y. Y., K. N., J. S. R.]; Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287 [C. M. E., W. B. I.]; and Cell Culture Laboratory, Children’s Hospital of Michigan, Detroit, Michigan 48201 [B. H.]

Research into molecular and genetic mechanisms underlying familial prostate cancer would be greatly advanced by in vitro models of prostate tumor cells representing primary tumors. We have successfully established an immortalized human prostate epithelial cell culture derived from primary tumors of familial prostate cancer patients with telomerase. The actively proliferating early-passaged 957E cells were transduced through infection with a retrovirus expressing the human telomerase catalytic subunit, human telomerase reverse transcriptase (hTERT). A high level of telomerase activity was detected in 957E/hTERT cells, but not in 957E cells. 957E/hTERT cells are currently growing well at passage 40, whereas 957E cells senesced at passage 5. 957E/hTERT cells exhibit epithelial morphology. Expression of an androgen-regulated prostate specific homeobox gene NKX3.1 and an epithelial cell-specific cytokeratin 8, but not prostate specific antigen or androgen receptor, was detected in 957E/hTERT cells. Prostatic stem cell antigen and p16 were also expressed in this line. 957E/hTERT cells showed growth inhibition when exposed to retinoic acid and transforming growth factor ß1, potent inhibitors of prostate epithelial cell growth. Chromosome analysis showed that the 957E/hTERT cell line (passage 10) was near diploid human male (XY), with most chromosome counts in the 44–46 range. However, there was random loss of chromosomes 8, 13, X, Y, and alteration in chromosome 4q. The late passage 957E/hTERT cell line (passage 32) was karyologically similar to the early passage 957E/hTERT cell line (passage 10) and also had the same alteration of 4q observed in the early passage 957E/hTERT cell line (passage 10) as well as a trisomy of chromosome 20. The well-characterized human cancer lines derived from such patients will be useful for the identification and characterization of prostate cancer susceptibility genes. This is the first documented case of an established human prostate cancer cell line from primary tumor of a familial prostate cancer patient.

This article has been cited by other articles:

				B. Bhatia, M. Jiang, M. Suraneni, L. Patrawala, M. Badeaux, R. Schneider-Broussard, A. S. Multani, C. R. Jeter, T. Calhoun-Davis, L. Hu, et al. Critical and Distinct Roles of p16 and Telomerase in Regulating the Proliferative Life Span of Normal Human Prostate Epithelial Progenitor Cells J. Biol. Chem., October 10, 2008; 283(41): 27957 - 27972. [Abstract] [Full Text] [PDF]

				Y. He, O. E. Franco, M. Jiang, K. Williams, H. D. Love, I. M. Coleman, P. S. Nelson, and S. W. Hayward Tissue-Specific Consequences of Cyclin D1 Overexpression in Prostate Cancer Progression Cancer Res., September 1, 2007; 67(17): 8188 - 8197. [Abstract] [Full Text] [PDF]

				G. Gu, J. Yuan, M. Wills, and S. Kasper Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo Cancer Res., May 15, 2007; 67(10): 4807 - 4815. [Abstract] [Full Text] [PDF]

				G. Farnie, R. B. Clarke, K. Spence, N. Pinnock, K. Brennan, N. G. Anderson, and N. J. Bundred Novel Cell Culture Technique for Primary Ductal Carcinoma In Situ: Role of Notch and Epidermal Growth Factor Receptor Signaling Pathways J Natl Cancer Inst, April 18, 2007; 99(8): 616 - 627. [Abstract] [Full Text] [PDF]

				I. V. Litvinov, D. J. Vander Griend, Y. Xu, L. Antony, S. L. Dalrymple, and J. T. Isaacs Low-Calcium Serum-Free Defined Medium Selects for Growth of Normal Prostatic Epithelial Stem Cells. Cancer Res., September 1, 2006; 66(17): 8598 - 8607. [Abstract] [Full Text] [PDF]

				S. Volik, B. J. Raphael, G. Huang, M. R. Stratton, G. Bignel, J. Murnane, J. H. Brebner, K. Bajsarowicz, P. L. Paris, Q. Tao, et al. Decoding the fine-scale structure of a breast cancer genome and transcriptome Genome Res., March 1, 2006; 16(3): 394 - 404. [Abstract] [Full Text] [PDF]

				S. Dalrymple, L. Antony, Y. Xu, A. R. Uzgare, J. T. Arnold, J. Savaugeot, L. J. Sokoll, A. M. De Marzo, and J. T. Isaacs Role of Notch-1 and E-Cadherin in the Differential Response to Calcium in Culturing Normal versus Malignant Prostate Cells Cancer Res., October 15, 2005; 65(20): 9269 - 9279. [Abstract] [Full Text] [PDF]

				P. Dalerba, C. Guiducci, P. L. Poliani, I. Cifola, M. Parenza, M. Frattini, G. Gallino, I. Carnevali, I. Di Giulio, S. Andreola, et al. Reconstitution of Human Telomerase Reverse Transcriptase Expression Rescues Colorectal Carcinoma Cells from In vitro Senescence: Evidence against Immortality as a Constitutive Trait of Tumor Cells Cancer Res., March 15, 2005; 65(6): 2321 - 2329. [Abstract] [Full Text] [PDF]