Involvement of protein kinase C in the growth regulation of human breast cancer cells.

Abstract

The relationship between growth of breast cancer and endocrine regulatory mechanisms is well established [1, 2, 3, 4, 5, 6, 7]. Numerous studies provided evidence for a distinct and important role of estrogen and progesterone and their receptors (ER and PR) in the growth regulation of human breast cancer (HBC) [1, 2, 3, 4, 5, 6, 7]. At present there is no unifying hypothesis about specific alterations that lead to the initiation and progression of HBC [5, 6, 7]. However, it is clear that human breast cancer progresses from an estrogenresponsive (hormone-dependent) ER+ tumor to a more aggressive estrogenunresponsive (hormone-independent) ER- phenotype that is less or poorly amenable to endocrine therapy [1, 2, 3, 4, 5, 6, 7]. Since only few hormone-independent HBC tumors lack the ER, the loss of the ER cannot explain the lack of antiestrogen sensitivity [1, 2, 3, 4, 5, 6, 7]. Despite many studies, the molecular mechanisms by which steroid hormones regulate the growth of both normal mammary and tumor cells remain elusive. It has been proposed that the escape from estrogen-dependent growth of HBC cells is due, at least in part, to alterations in their autocrine and/or paracrine growth mechanisms [16, 17, 18, 19, 20, 21, 22, 23]. Consequently, disordered secretion of growth factors (GFs) from HBC cells and/or surrounding stromal and other cells may result in a permanent activation of intracellular signaling pathways contributing in the bypass of the estrogen-dependent growth control of HBC cells and hence progression of the disease.