Transdifferentiation of NRP-152 rat prostatic basal epithelial cells toward a luminal phenotype: regulation by glucocorticoid, insulin-like growth factor-I and transforming growth factor-beta.
The role of basal epithelial cells in prostatic function, development and carcinogenesis is unknown. The ability of basal prostatic epithelial cells to acquire a luminal phenotype was explored in vitro using the NRP-152 rat dorsal-lateral prostate epithelial cell line as a model system. NRP-152, which was spontaneously immortalized and clonally derived, is an androgen-responsive and nontumorigenic cell line that has a basal cell phenotype under normal growth conditions. However, when placed in mitogen-deficient media, these cells undergo a dramatic morphological change to a luminal phenotype. Under these growth-restrictive conditions, immunocytochemical analysis shows that NRP-152 cells acquire the luminal markers Z0-1 (a tight-junction associated protein), occludin (integral tight-junction protein), and cytokeratin 18, and lose the basal markers cytokeratins 5 and 14. Total protein and mRNA levels of cytokeratins 8, 18, c-CAM 105 (the calcium-independent cell adhesion molecule) and Z0-1, as detected by western and/or northern blot analyses, respectively, are induced, while cytokeratin 5 and 15 are lost, and occludin is unchanged. Concomitant with this differentiation, expression of transforming growth factor-beta2 (TGF-beta2), TGF-beta3, and TGF-beta receptor type II (TbetaRII) is induced, while those of TGF-beta1 and TbetaRI remain essentially unchanged. Mitogens, such as insulin-like growth factor-I and dexamethasone inhibit luminal differentiation, while exogenous TGF-beta induces such differentiation. These data together with TGF-beta neutralization experiments using pan-specific antibody implicate an important role for autocrine TGF-beta in the induction of the luminal differentiation.
Danielpour
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Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010641:Phenotype; D011467:Prostate / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
D015415:Biomarkers; D005938:Glucocorticoids; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone