Study Title:

Vitamin D Helps Prevent Breast Cancer

Study Abstract

Numerous studies have shown that the active form of vitamin D, 1,25(OH)2D3, can exert growth inhibitory effects on human breast cancer cells and mammary tumor growth. However, the molecular mechanisms remain to be fully delineated. This study demonstrates for the first time that CCAAT enhancer-binding protein (C/EBP), a member of the C/EBP family of transcription factors, is induced by 1,25(OH)2D3 and is a potent enhancer of VDR transcription in MCF-7 breast cancer cells. 1,25(OH)2D3 was found to induce C/EBP as well as VDR expression in MCF-7 cells. C/EBP was not detected in MDA-MB-231 cells that are poorly responsive to 1,25(OH)2D3. Antiproliferative effects of 1,25(OH)2D3 and induction of VDR were observed in MDA-MB-231 cells transfected with C/EBP, and knockdown of C/EBP suppressed VDR and antiproliferative effects of 1,25(OH)2D3 in MCF-7 cells. Transfection of C/EBP in MCF-7 cells resulted in a dose-dependent enhancement of hVDR transcription. Our studies show that C/EBP can bind to Brahma (Brm), an ATPase that is a component of the SWI/SNF complex, and cooperate with Brm in the regulation of hVDR transcription in MCF-7 cells. Because the levels of VDR in MCF-7 breast cancer cells correlate with the antiproliferative effects of 1,25(OH)2D3 and because C/EBP has been suggested as a potential tumor suppressor in breast cancer, these findings provide important mechanisms whereby 1,25(OH)2D3 may act to inhibit growth of breast cancer cells. These findings also identify C/EBP as a 1,25(OH)2D3 target in breast cancer cells and provide evidence for C/EBP as a candidate for breast cancer treatment.

From press release:

Calcitrol, the active form of vitamin D, has been found to induce a tumor suppressing protein that can inhibit the growth of breast cancer cells, according to a study by researcher Sylvia Chistakos, Ph.D., of the UMDNJ-New Jersey Medical School.

Chistakos, a professor of biochemistry, has published extensively on the multiple roles of vitamin D, including inhibition of the growth of malignant cells found in breast cancer. Her current findings on the vitamin D induced protein that inhibits breast cancer growth are published in a recent issue of The Journal of Biological Chemistry.

Previous research had determined that increased serum levels of vitamin D are associated with an improved diagnosis in patients with breast cancer. Prior to the current study, little was known about the factors that determine the effect of calcitrol on inhibiting breast cancer growth, she said.

During the study, Christakos and co-author Puneet Dhawan, Ph.D., examined the protein involved in the action that can reduce the growth of vitamin D in breast cancer cells. “These results provide an important process in which the active form of vitamin D may work to reduce growth of breast cancer cells,” said Christakos. “These studies provide a basis for the design of new anticancer agents that can target the protein as a candidate for breast cancer treatment.”

Study Information

Puneet Dhawan, Robert Weider, and Sylvia Christakos.
CCAAT Enhancer-binding Protein Is a Molecular Target of 1,25-Dihydroxyvitamin D3 in MCF-7 Breast Cancer Cells.
The Journal of Biological Chemistry
2009 January
Department of Biochemistry and Molecular Biology and the Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103.

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