PMID- 7686167 OWN - NLM STAT- MEDLINE DCOM- 19930727 LR - 20181130 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 156 IP - 1 DP - 1993 Jul TI - Pretreatment with vitamin A inhibits transforming growth factor alpha stimulation of human mammary carcinoma cells. PG - 80-7 AB - 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. FAU - Halter, S A AU - Halter SA AD - Department of Pathology, Vanderbilt University, Nashville, Tennessee. FAU - Winnier, A R AU - Winnier AR FAU - Arteaga, C L AU - Arteaga CL LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor alpha) RN - 11103-57-4 (Vitamin A) RN - 21820-51-9 (Phosphotyrosine) RN - 42HK56048U (Tyrosine) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Breast Neoplasms/*pathology MH - Cell Division/*drug effects MH - ErbB Receptors/metabolism MH - Female MH - Gene Expression/drug effects MH - Humans MH - In Vitro Techniques MH - Phosphotyrosine MH - RNA, Messenger/genetics MH - Signal Transduction/drug effects MH - Transforming Growth Factor alpha/*antagonists & inhibitors/metabolism MH - Tumor Cells, Cultured MH - Type C Phospholipases/metabolism MH - Tyrosine/analogs & derivatives/metabolism MH - Vitamin A/*pharmacology EDAT- 1993/07/01 00:00 MHDA- 1993/07/01 00:01 CRDT- 1993/07/01 00:00 PHST- 1993/07/01 00:00 [pubmed] PHST- 1993/07/01 00:01 [medline] PHST- 1993/07/01 00:00 [entrez] AID - 10.1002/jcp.1041560112 [doi] PST - ppublish SO - J Cell Physiol. 1993 Jul;156(1):80-7. doi: 10.1002/jcp.1041560112.