Pretreatment with vitamin A inhibits transforming growth factor alpha stimulation of human mammary carcinoma cells

Abstract

Vitamin A or retinol is an important agent in the normal differentiation and growth of cells. Retinol is an effective inhibitor of the growth of many transformed cells in vitro and in vivo but its mechanism of action is unclear. Transforming growth factor alpha (TGF alpha) is a known mitogen. We examined the effect of retinol treatment on TGF alpha stimulation of two human mammary carcinoma cell lines, one which is growth inhibited by retinol and one which is not. Pretreatment of both cell lines for 48 hours with retinol resulted in inhibition of TGF alpha stimulation of growth. In the T47D cell line the mechanism was not related to an effect on the cellular content of TGF alpha, epidermal growth factor (EGF) receptor protein, EGF receptor mRNA, or on the binding of TGF alpha to the EGF receptor. However, TGF alpha-induced stimulation of the EGF receptor substrate, phospholipase C-gamma 1, was abrogated in the T47D cell line with retinol pretreatment. In the MDA-MB-468 cell line, pretreatment with retinol resulted in a decrease in tyrosine phosphorylation of the EGF receptor. These results suggest that pretreatment with retinol decreases cellular proliferation seen with TGF alpha treatment by altering phospholipase C-gamma 1 response and/or EGF receptor tyrosine kinase activity. Alteration of phospholipase C-gamma 1 activity does not appear to be responsible for the inhibition of cell growth seen in the absence of TGF alpha stimulation.

Metabolic conversion of retinol to retinoic acid mediates the biological responsiveness of human mammary epithelial cells to retinol

“…Mammary carcinoma cells are responsive to ROH (Halter et al, 1993; Lacroix and Lippman, 1980; Ueda et al, 1980) and RA (Agadir et al, 1999; Takatsuka et al, 1996), exhibiting dose‐dependent reductions in proliferation. While it is known that tRA also inhibits the growth of normal mammary cells (Lee et al, 1995; Seewaldt et al, 1997), the role of ROH in growth regulation of normal mammary cells remains to be ascertained.…”

Inhibition of cellular proliferation and modulation of insulin-like growth factor binding proteins by retinoids in a bovine mammary epithelial cell line

“…Thus, RA is a potent but transient inhibitor of bovine mammary epithelial cell proliferation, and this growth inhibition is correlated with increased IGFBP-2 accumulation and inhibition of IGF-I-stimulated IGFBP-3 protein secretion. Retinoids inhibit the proliferation of many mammary carcinoma cell lines (Fontana et al, 1991;Adamo et al, 1992; Decensi et al, 1993;Halter et al, 1993;Shemer et al, 1993). However, our understanding of retinoid action in normal mammary epithelium is limited.…”