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Human cell lines as an in vitro/in vivo model for prostate carcinogenesis and progression
Author(s) -
Webber Mukta M.,
Quader Salmaan T.A.,
Kleinman Hynda K.,
BelloDeOcampo Diana,
Storto Patrick D.,
Bice Gillian,
DeMendoncaCalaca Wanderley,
Williams Daniel E.
Publication year - 2001
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.1041
Subject(s) - carcinogenesis , biology , prostate , cancer research , prostate cancer , pathology , cancer , tumor progression , androgen receptor , cell culture , immortalised cell line , medicine , genetics
BACKGROUND The study of prostate carcinogenesis and tumor progression is made difficult by the lack of appropriate in vitro and in vivo models. High prevalence of prostatic intra‐epithelial neoplasia and latent prostatic carcinoma, representing multiple steps in carcinogenesis to invasive carcinoma, are relevant targets for cancer prevention. From the RWPE‐1, immortalized, non‐tumorigenic, human prostate epithelial cell line, we have derived four tumorigenic cell lines with progressive malignant characteristics. METHODS Cell lines were derived by exposure of RWPE‐1 to N ‐methyl‐ N ‐nitrosourea (MNU), selected and cloned in vivo and in vitro, and characterized by prostatic epithelial and differentiation markers, karyotype analysis, anchorage‐independent growth, invasiveness, tumorigenicity, and pathology of the derived tumors. RESULTS Cytokeratins 8 and 18, androgen receptor, and prostate‐specific antigen expression in response to androgen, confirm prostatic epithelial origin. RWPE‐1 cells do not grow in agar and are not tumorigenic in mice, but the growth, tumorigenicity, and tumor pathology of the MNU cell lines correlate with their invasive ability. The WPE1‐NA22 (least malignant) form small, well‐differentiated, and WPE1‐NB26 cells (most malignant) form large, poorly differentiated, invasive tumors. Overall, loss of heterozygosity for chromosomes 7q, 13q, 18q, and 22, and gain of 5, 9q, 11q, and 20, was observed. The MNU cell lines, in order of increasing malignancy are; WPE1‐NA22, WPE1‐NB14, WPE1‐NB11, and WPE1‐NB26. CONCLUSIONS This family of cell lines with a common lineage represents a unique and relevant model which mimics stages in prostatic intra‐epithelial neoplasia (PIN) and progression to invasive cancer, and can be used to study carcinogenesis, progression, intervention, and chemoprevention. Prostate 47:1–13, 2001. © 2001 Wiley‐Liss, Inc.