2001 WHRG Grant Program

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Symposia

Association of IP₆-induced p27^Kip1
Up-Regulation and Differentiation
of Breast Cancer Cells

Ivana Vucenik, PhD
School of Medicine, University of Maryland, Baltimore

Inositol hexaphosphate (IP₆) is a common constituent of grains and cereals and an active component responsible for the anticancer effect of the high-fiber diet. A striking anticancer action of IP₆ has been demonstrated in various models, including breast cancer. In in vitro models, IP₆ inhibits tumor cell growth and increases differentiation of malignant cells, causing the cancer cells to mature, become less aggressive and behave like normal cells. However, the mechanism of this action is still not known.

Based on our preliminary data, we hypothesize that the anti-proliferative effects of IP₆ are mediated by up-regulation of p27^Kip1 through activation of protein kinase C (PKC)d. To test this hypothesis in this proposal, we are planning to address questions: (1) Is IP₆-induced activation of PKCd; involved in this up-regulation of p27^Kip1, and (2) How important is the up-regulation of the p27^Kip1 in the IP₆-induced differentiation?

The results of this proposal may have some potentially important therapeutic consequences, since (a) p27^Kip1 is a critical intrinsic brake of the cell cycle engine. Deregulation of p27^Kip1 expression is a relatively common feature of many solid tumors. Total or partial loss of p27^Kip1 expression in tumor cells may have important implications in breast cancer, since it has been shown that patients with high levels of p27^Kip1 have a good prognosis, compared to those with low levels; (b) Targeting some members of the PKC signal transduction pathways can be important in anti-tumor therapeutic strategy; and (c) Differentiation therapy could be offered as an alternate for the treatment of breast cancer.

Therefore, the proposed studies might have a great impact on the course of breast cancer, providing a basis for novel strategies and novel alternative therapeutic protocols in the treatment and prevention of this dreadful disease.