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Our studies have identified 1,25(OH)2D3 as a coordinate regulator of proliferation and apoptosis in breast cancer cells. In MCF-7 cells, 1,25(OH)2D3 down regulates the estrogen receptor (ER), suggesting that the effects of 1,25(OH)2D3 may be linked to disruption of estrogen regulated survival signals. Although studies have demonstrated that 1,25(OH)2D3 inhibits growth of ER negative breast cancer cells, previous data were generated by comparison of cell lines derived from heterogeneous human tumors and harboring diverse genetic alterations. To provide more conclusive evidence for independent growth regulatory pathways mediated by antiestrogens and 1,25(OH)2D3, we examined vitamin D3 sensitivity in MCf-7 cells selected for resistance to ICI 182, 780 (Zeneca, Macclesfield, UK). The clones we selected for resistance to ICI 182,780 retain functional VDR and undergo 1,25(OH)2D3 mediated growth arrest and apoptosis, in vitro and in vivo, despite loss of estrogen dependence. Cell cycle data indicate that treatment of parental or anti-estrogen resistant MCF-7 clones with 1,25(OH)2D3, in the presence or absence of ICI 182,780, increases the percentage of cells in G0/G1 while reducing the number of cells in S phase. In addition, 1,25(OH)2D3 induces characteristic features of apoptosis, including DNA fragmentation, in both parental and anti-estrogen resistant MCF-7 cells. Furthermore, we report that cells selected for vitamin D3 resistance retain sensitivity to ICI 182,780 mediated growth arrest and apoptosis. This work emphasizes that vitamin D3 compounds and anti-estrogens trigger growth arrest and apoptosis in breast cancer cells by distinct mechanisms, and that breast cancer cell sensitivity to 1,25(OH)2D3 is not diminished during the progression to estrogen independence.
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
June 1999,
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
January 1999,
Breast cancer research and treatment,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
December 2002,
Journal of molecular endocrinology,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
January 1997,
Oncology research,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
March 1998,
The Journal of biological chemistry,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
December 2016,
Phytotherapy research : PTR,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
July 2000,
Biochemical and biophysical research communications,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
January 2007,
The Journal of steroid biochemistry and molecular biology,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
February 2007,
Cancer chemotherapy and pharmacology,
E Nolan, and
M Donepudi, and
K VanWeelden, and
L Flanagan, and
J Welsh
November 2000,
The Journal of steroid biochemistry and molecular biology,
