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Control of Breast Tumor Cell Growth by Dietary Indoles

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Annual rept. 1 Sep 1996-21 Aug 1997

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Indole-3-carbinol I3C, a naturally occurring component of Brassica vegetables has been shown to reduce the incidence of mammary tumors. Our studies of the molecular mechanisms and signal transduction pathways by which I3C mediates its antiproliferative effects have established that I3C can induce a reversible G1 cell cycle arrest of cultured human breast cancer cells MCF7 cells in the absence of estrogen receptor signaling. This cell cycle arrest is accompanied first by a rapid inhibition of expression of the cyclin dependent kinase-6 CDK6 cell cycle component and later by a stimulation in production of both the p21 and the p27 CDK inhibitors. Importantly, these I3C-mediated effects functionally alter the ability of G1-acting CDK2 and CDK6 to phosphorylate the Rb tumor suppressor protein, which is a necessary event for cell cycle progression. We have also shown that while I3C products possess significant cytostatic activity against the estrogen-induced growth of MCF7 cells, their activities in estrogen-responsive reporter genes are highly dependent on the gene construct, suggesting that the indoles do not function as classical estrogen antagonists in these studies. Instead, the indoles may function by activation of other genes central to the regulation of estrogen-induced cellular responses.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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