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Primary culture model of peroxisome proliferator‐activated receptor γ activity in prostate cancer cells
Author(s) -
Xu Yue,
Iyengar Sunita,
Roberts Richard L.,
Shappell Scott B.,
Peehl Donna M.
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10281
Subject(s) - peroxisome proliferator activated receptor , cancer research , biology , prostate cancer , cancer cell , cell culture , nuclear receptor , cell growth , microbiology and biotechnology , thiazolidinedione , endocrinology , receptor , medicine , transcription factor , cancer , biochemistry , type 2 diabetes , genetics , gene , diabetes mellitus
BRL 49653 (rosiglitazone) is a thiazolidinedione anti‐diabetic drug that activates the nuclear receptor, peroxisome proliferator‐activated receptor gamma (PPARγ). Pilot clinical trials have shown evidence of therapeutic activity of PPARγ agonists against prostate cancer. To more effectively use PPARγ ligands to treat this common and generally chemo‐resistant type of cancer, it will be necessary to better understand the nature of PPARγ activity in prostate cancer cells. Tumor suppressor effects of activation of PPARγ may include suppression of growth and/or induction of differentiation or apoptosis. We investigated responses of primary cultures of human prostatic cancer cells to BRL 49653. PPARγ was expressed in all of the cell strains examined. BRL 49653 caused dose‐ and time‐dependent growth inhibition that was associated with increased expression of the transcription repressor, transforming growth factor β‐stimulated clone 22 (TSC‐22), and markedly increased expression of the secretory differentiation‐associated gene adipophilin . Adipocyte‐type fatty acid binding protein (aFABP), neutrophil gelatinase‐associated lipocalin (NGAL), glycerol kinase (GyK), and β‐catenin, which are regulated by PPARγ ligands in certain other types of cells, were not regulated by BRL 49653 in prostate cells. Upregulation of adipophilin coincided with morphological changes and the appearance of cytoplasmic vacuoles with ultrastructural features of secondary lysosomes. These results extend previous studies with established cancer cell lines and show that PPARγ agonists can inhibit proliferation and modulate expression of secretory‐associated genes in primary cultures of prostate cancer cells, further warranting consideration of these agents as pro‐differentiating chemotherapeutic or chemoprevention agents for the treatment of prostate cancer. © 2003 Wiley‐Liss, Inc.