Carcinogenesis Advance Access published online on November 27, 2006
Carcinogenesis, doi:10.1093/carcin/bgl230
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1 IIT Research Institute, Chicago, IL, 60616
* To whom correspondence should be addressed. 1
Received June 12, 2006
Revised November 13, 2006
Accepted November 17, 2006
CANCER PREVENTION
Overexpression of ER and VDR is not sufficient to make ER-negative MDA-MB231 breast cancer cells responsive to 1
Xinjian Peng 1, Pavan Jhaveri 2, Erum A. Hussain-Hakimjee 2, and Ranjendra G. Mehta 1 *
-Hydroxyvitamin D5
2 University of Illinois at Chicago, Chicago, IL, 60612
Ranjendra G. Mehta, E-mail: rmehta{at}iitri.org
Abstract 
-hydroxy vitamin D5 (1(OH)D5) is an active vitamin D analog showing promising chemopreventive effect in breast cancer carcinogenesis. We previously reported that Estrogen receptor (ER)-positive breast cancer cells were sensitive, whereas ER-negative breast cancer cells were relatively resistant to its antiproliferative effects. In the present study, we used ER-negative MDA-MB231, ER-transfected MDA-MB231 (S30) and ER-positive BT474 cell lines to evaluate the possible association between ER status and cellular sensitivity to 1(OH)D5 treatment. Our results demonstrate that ER expression in ER-negative breast cancer cells (S30) did not increase the sensitivity to 1(OH)D5, whereas in ER-positive BT474 cells, the significant antiproliferative effect of 1(OH)D5 was correlated with the downregulation of ER and progesterone receptor (PgR) expression. Further analysis indicated that both MDA-MB231 and S30 cells express low VDR at transcriptional level and protein level. However, transfection of VDR failed to restore the sensitivity to 1(OH)D5 in MDA-MB231 and S30 cells, although VDR direct target gene CYP24 was more responsive to 1(OH)D5 treatment in MDA-MB231 and S30 cells overexpressing VDR. In addition, nuclear receptor cofactors NCoR1 and SRC1 that could potentially affect VDR action were also low in both MDA-MB231 and S30 cells in comparison to ER-positive, vitamin D sensitive BT474 cells. These results suggest that in addition to the increased ER and VDR expression, the intact VDR signaling machinery as present in ER-positive, vitamin D sensitive cells is essential for the antiproliferative action of vitamin D, whereas the direct VDR target genes such as CYP24 can remain responsive to augmented VDR expression.
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