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Development and Characterization of DP-153, a Nontumorigenic Prostatic Cell Line That Undergoes Malignant Transformation by Expression of Dominant-negative Transforming Growth Factor ß Receptor Type II¹

Ireland Cancer Center Research Laboratories and the Department of Pharmacology, Case Western Reserve University/University Hospital of Cleveland, Cleveland, Ohio 44106

We have developed a nontumorigenic epithelial cell line, DP-153, from the dorsal prostate of a Lobund/Wistar rat treated with N-methyl-N-nitrosourea and testosterone propionate. DP-153 cells express cytokeratins 5 and 14, but not cytokeratin 18, consistent with a basal epithelial cell phenotype. Similar to the nontumorigenic NRP-152 prostatic cell line, DP-153 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic cells. They express prostatic acid phosphatase and androgen receptors and require several mitogens (epidermal growth factor, insulin, dexamethasone, and cholera toxin) for sustained growth in culture under serum-containing conditions. DP-153 cells are also growth-stimulated by keratinocyte growth factor and basic fibroblast growth factor and growth-inhibited by all-trans-retinoic acid, 1,25-dihydroxyvitamin D₃, and transforming growth factor (TGF)-ß1. We demonstrate that expression of dominant-negative TGF-ß receptor type II by retroviral transduction of DP-153 cells leads to complete loss of TGF-ß1-induced growth inhibition. When transplanted s.c. in athymic mice, DP-153 cells expressing dominant-negative TGF-ß receptor type II form tumors as early as 4 weeks, in contrast to the vector control and parental cell line, which do not form tumors even 8 months after transplantation, supporting the observation that TGF-ß functions as a tumor suppressor in these cells. Our data further support that DP-153 is a suitable cell line for analysis of normal prostatic growth and carcinogenesis.

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