p53 Is Required for 1,25-Dihydroxyvitamin D3-Induced G0 Arrest But Is Not Required for G1 Accumulation or Apoptosis of LNCaP Prostate Cancer Cells

• Published in: Endocrinology (Philadelphia) 2003-01, Vol.144 (1), p.50-60
• Main Authors: Polek, Tara C, Stewart, LaMonica V, Ryu, Elizabeth J, Cohen, Michael B, Allegretto, Elizabeth A, Weigel, Nancy L
• Format: Article
• Language: English
• Subjects: Accumulation; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Calcitriol; Calcitriol - pharmacology; Carcinogenesis, carcinogens and anticarcinogens; Cell cycle; Cell Division - drug effects; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - metabolism; Drug Synergism; Foods and miscellaneous; G1 Phase - drug effects; Humans; Ki-67 Antigen - analysis; Male; Medical sciences; p53 Protein; Prostate cancer; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-bcl-2 - analysis; Resting Phase, Cell Cycle - drug effects; Retinoic acid; Synergism; Tretinoin - pharmacology; Tumor cell lines; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - physiology; Tumors; Vitamin D3
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2001-210109

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] is an effective agent for inhibiting the growth of prostate cancer cells including LNCaP and PC-3 cell lines. However, the extent of growth inhibition in these cell lines differs because LNCaP cells are much more responsive than PC-3 cells. Previous studies in LNCaP cells have shown that 1,25-(OH)2D3 treatment results in G0/G1 cell cycle accumulation, loss of Ki67 expression, and induction of apoptosis. One difference between the two cell lines is that PC-3 cells lack functional p53, a protein that plays roles both in cell cycle regulation and induction of apoptosis. In this study, the role of p53 in 1,25-(OH)2D3 action was examined using the p53-negative PC-3 cells and a line of LNCaP cells, called LN-56, in which p53 function was shut off using a dominant negative p53 fragment. We found that treatment with 1,25-(OH)2D3 extensively inhibits growth of LN-56 prostate cancer cells lacking p53, but in contrast to the parental LNCaP cells, the LN-56 cells recover rapidly. Moreover, in prostate cancer cells, the synergism between 1,25-(OH)2D3 and 9-cis retinoic acid appears to be dependent on the presence of functional p53; however, 1,25-(OH)2D3-mediated induction of G1 cell cycle accumulation and induction of apoptosis is not.