A New Cell Line Expressing A Novel Type Of TMPRSS2-ERG Gene Fusion Derived From Primary Tumors Of Familial Prostate Cancer Patient

Main Category: Urology / Nephrology
Also Included In: Prostate / Prostate Cancer;  Cancer / Oncology
Article Date: 12 Jun 2008 - 5:00 PDT

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ORLANDO, FL (UroToday.com) - Recent studies have established that a high proportion of prostate cancer harbors a gene fusion between the androgen regulated TMPRSS2 gene and the ETS genes ERG, ETV1 or ETV4. However in vitro model representing primary tumors to study the molecular mechanisms and functional consequences of this important chromosomal rearrangement are currently limited and are greatly needed.

In this study, the tumor tissue (RC-123T) used for generating the RC-123T/E cell line with HPV-16 E6E7 genes was obtained from a 57 year old familial prostate cancer patient who had well differentiatied adenocarcinoma (Gleason 3+3). The cell line was characterized phenotypically and cytogenically. Dual color fluorescence in situ hyb ridization (FISH) assay was used to test for ERG (3' 5') break-aparts, and for translocation of TMPRSS2 and ERG and ETV1, in both interphase nuclei as well as metaphases. The cells were also characterized for putative stem cell markers CD133, SOX2 and prostate cell markers by immunohistochemistry and RT-PCR.

The investigators have successfully established an immortalized human prostate epithelial cell culture derived from primary tumors of familial prostate cancer patients carrying TMPRSS2-ERG fusion genes with HPV16 E6E7 genes (RC-123T/E). RC-123T/E cells are currently growing well at passage 30, whereas RC-123T cells senesced at passage 5. Expresison of an androgen-regulated prostate specific homeobox gene NKX3.1, the epithelial cell-specific cytokeratin 8 and RC-123T/E cells. TMPRSS2-ERG genes were also expressed in this line. The RC-123T/E cells formed spheres under suspension culture and branched differentiated in matrigel. The RC-123T/E cells also expressed putative stem cell markers CD133 and SOX2. Interestingly, the FISH analysis showed the translocation of chromosome t(7;21)(q21:q21) in the RC-123T/E cell line and also in its primary tumor tissue.

They conclude that the RC-123T/E cell line and its primary tumor tissue possess the translocation of TMPRSS2/ERG to chromosome 7q which adds another class of gene arrangement in prostate cancer. In addition, this cell line expressed putative stem cell markers and TMPRSS2-ERG gene fusion. This model provides a novel tool to study the cellular and molecular mechanisms of TMPRSS2-ETS genes in prostate cancer.

Presented by Hongzhen Li, MD, et al., at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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