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Induction of apoptosis in androgen‐independent mouse mammary cell line by 1, 25‐dihydroxyvitamin D 3
Author(s) -
Furuya Yuzo,
Ohta Sho,
Shimazaki Jun
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960927)68:1<143::aid-ijc25>3.0.co;2-b
Subject(s) - apoptosis , androgen , programmed cell death , dna fragmentation , biology , endocrinology , medicine , androgen receptor , cell culture , cancer research , testosterone (patch) , cell cycle , fragmentation (computing) , hormone , prostate cancer , cancer , biochemistry , genetics , ecology
Androgen‐dependent tumors eventually progress to independent‐tumors after androgen withdrawal. Effective treatment for hormone‐independent tumors is therefore needed. Androgen‐independent CS‐2 cells could grow in serum‐free culture whether androgen is present in the medium or not. In the present study, the mechanism of cell death in CS‐2 cells was examined after 1, 25‐dihydroxyvitamin D 3 [1, 25(OH) 2 D 3 ] treatment. 1, 25(OH) 2 D 3 has been examined as an anti‐tumor agent, but its role in promoting cell death is poorly understood. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, the cells underwent apoptosis with 1, 25(OH) 2 D 3 treatment. Northern‐blot analysis was used to identify a series of genes whose expression per cell is enhanced during the apoptotic pathway. In the apoptotic process induced by 1, 25(OH) 2 D 3 , mRNA expression of testosterone‐repressed prostatic message 2, transforming growth factor β1, glucose‐regulated 78‐kDa protein and calmodulin increased. Flow‐cytometric analysis showed that 1, 25(OH) 2 D 3 treatment resulted in a block in G 0 /G 1 of the cell cycle. These results demonstrate that androgen‐independent CS‐2 cells retain the ability to undergo apoptosis by 1, 25(OH) 2 D 3 . This system appears to be a good model for investigating apoptosis of hormone‐independent cancer. © 1996 Wiley‐Liss, Inc.