Molecular cytogenetic studies of a serially transplanted primary prostatic carcinoma xenograft (CWR22) and four relapsed tumors

Kochera, Mary; Depinet, Theresa W.; Pretlow, Theresa P.; Giaconia, Joseph M.; Edgehouse, Nancy L.; Pretlow, Thomas G.; Schwartz, Stuart

doi:10.1002/(sici)1097-0045(19990915)41:1<7::aid-pros2>3.0.co;2-1

Cited by 13 publications

(9 citation statements)

References 14 publications

(21 reference statements)

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“…In summary, our results of the G-banding and the ploidy analysis of the CWR22Pc cells are in line with the mosaic karyotype reported previously for the primary CWR22P tumors (6, 14), the recurrent CWR22R xenografts (14) and the CWR22Rv1 cell line established from the recurrent CWR22R tumors (8). In detail, primary CWR22 xenograft tumors were reported to have a mixture of two karyotypes where part of the cells displayed an unidentified marker chromosome (6).…”

Section: Resultssupporting

confidence: 91%

“…In detail, primary CWR22 xenograft tumors were reported to have a mixture of two karyotypes where part of the cells displayed an unidentified marker chromosome (6). In addition, the relapsed strains of CWR22R tumors after androgen deprivation showed each a different karyotype (14), and the CWR22Rv1 cell line consists of a mixed population of hyperdiploid (90%) and near-tetraploid (10%) cells (15). The results of our study reported here indicated a mosaic karyotype of CWR22Pc cells.…”

Section: Resultsmentioning

confidence: 99%

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Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor

Dagvadorj

Tan²,

Liao³

et al. 2008

Clinical Cancer Research

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Purpose: One of the major obstacles in understanding the molecular mechanisms underlying the transition of prostate cancer growth from androgen dependency to a hormone-refractory state is the lack of androgen-regulated and tumorigenic human prostate cancer cell lines. Experimental Design: We have established and characterized a new human prostate cancer cell line, CWR22Pc, derived from the primary CWR22 human prostate xenograft tumors. Results: The growth of CWR22Pc cells is induced markedly by dihydrotestosterone, and CWR22Pc cells express high levels of androgen receptor (AR) and prostate-specific antigen (PSA). Importantly, PSA expression in CWR22Pc cells is regulated by androgens. Stat5a/b, Stat3, Akt, and mitogen-activated protein kinase were constitutively active or cytokine inducible in CWR22Pc cells. The AR in CWR22Pc cells contains the H874Y mutation, but not the exon 3 duplication or other mutations. When inoculated subcutaneously into dihydrotestosteronesupplemented castrated nude mice, large tumors formed rapidly in 20 of 20 mice, whereas no tumors developed in mice without circulating dihydrotestosterone. Moreover, the serum PSA levels correlated with the tumor volumes.When androgens were withdrawn from the CWR22Pc tumors grown in nude mice, the tumors initially shrank but regrew back as androgen-independent tumors. Conclusions: This androgen-regulated and tumorigenic human prostate cancer cell line provides a valuable tool for studies on androgen regulation of prostate cancer cells and on the molecular mechanisms taking place in growth promotion of prostate cancer when androgens are withdrawn from the growth environment. CWR22Pc cells also provide a model system for studies on the regulation of transcriptional activity of mutated H874YAR in a prostate cancer cell context.The median duration of response to androgen deprivation therapy of primary prostate cancer is less than 3 years (1, 2). The molecular mechanisms underlying development of androgen-independent growth of prostate cancer are largely unknown and no effective therapies for hormone-refractory prostate cancer exist at present. One of the key problems in conducting studies to identify growth factors and signaling pathways that can replace androgens in the growth control of prostate cancer cells is the lack of androgen receptor (AR) -positive human prostate cancer cell lines that are regulated by androgens and would be tumorigenic in nude mice. LNCaP cells respond by accelerated growth rate to androgens (3), but are able to grow relatively well in the absence of androgens (4). Moreover, tumor incidence of LNCaP cells after s.c. inoculation into nude mice is low and the tumors grow slowly (3).We have characterized a new human prostate cancer cell line established from primary transplantable human CWR22 prostate tumors. CWR22 tumors were originally derived from a Gleason score 9 primary prostate cancer with bone metastases (5, 6). The primary CWR22 prostate tumors are highly responsive to androgen deprivation with marked tumor regres...

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor

Dagvadorj

Tan²,

Liao³

et al. 2008

Clinical Cancer Research

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“…CWR-R1 is also derived from a recurrent CWR22 tumor, but no subline information is available [50]. CWR22R-2152 contained a balanced reciprocal translocation, t(6;14)(q15;q32) that was not detected in CWR22 nor in any of the other described CWR22R xenograft sublines [59]. This translocation was detected in both 22Rv1 and CWR-R1 cells, suggesting that both are derived from the same sublineage as CWR22R-2152.…”

Section: Cytogenetic Analysismentioning

confidence: 99%

Molecular characterization of human prostate carcinoma cell lines

et al. 2003

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“…23,24,27 The cells from CWR22 xenografts (ϳ10 6 ) in 50% Matrigel (Becton Dickinson, Bedford, MA) were implanted into the flanks of male NCr nude mice (Taconic, Germantown, NY), which were supplemented with 12.5 mg of sustained-releasing testosterone pellets (Innovative Research of America, Sarasota, FL). When the tumors were established and reached the size of 1 cm in largest dimension, the host mice were castrated and the testosterone pellets removed.…”

Section: Cwr22 Xenografts and Cell Linesmentioning

confidence: 99%

Androgen Receptor Remains Critical for Cell-Cycle Progression in Androgen-Independent CWR22 Prostate Cancer Cells

Yuan

Wang

et al. 2006

The American Journal of Pathology

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The majority of prostate cancers (PCa) that relapse after androgen deprivation therapy (androgen-independent PCa) continue to express androgen receptor (AR). To study the functional importance of AR in these tumors , we derived androgen-independent CWR22 PCa xenografts in castrated mice and generated a cell line from one of these xenografts (CWR22R3). Similarly to androgen-independent PCa in patients , the relapsed xenografts and cell line expressed AR and were resistant to treatment with bicalutamide. However , expression of the ARregulated PSA gene in the CWR22R3 cell line was markedly decreased compared to the relapsed xenografts in vivo. Transfections with androgenregulated reporter genes further indicated that the cells lacked androgen-independent AR transcriptional activity and were not hypersensitive to low androgen concentrations despite constitutive activation of the Erk/MAP kinases. Nonetheless , AR remained essential for androgen-independent growth because retroviral shRNA-mediated AR down-regulation resulted in marked long-term growth suppression. This was associated with increased levels of p27 kip1 and hypophosphorylation of retinoblastoma protein but not with decreases in D-type cyclin levels or MAP kinase activation. These results reveal a potentially critical function of AR in androgen-independent PCa that is distinct from its previously described transcriptional or nontranscriptional functions.

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Molecular cytogenetic studies of a serially transplanted primary prostatic carcinoma xenograft (CWR22) and four relapsed tumors

Cited by 13 publications

References 14 publications

Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor

Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor

Molecular characterization of human prostate carcinoma cell lines

Androgen Receptor Remains Critical for Cell-Cycle Progression in Androgen-Independent CWR22 Prostate Cancer Cells

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