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Tyrosine kinase inhibition decreases Muc‐1 expression in mouse epithelial cells
Author(s) -
Wegner Carole C.,
Zhou Xinhui,
Ding ZhiMing,
Kuo Macus T.,
Carson Daniel D.
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199702)170:2<200::aid-jcp12>3.0.co;2-l
Subject(s) - biology , signal transduction , tyrosine kinase , microbiology and biotechnology , tyrosine phosphorylation , gene expression , second messenger system , staurosporine , protein kinase c , biochemistry , gene
Mouse uterine epithelial cells (UEC) express high levels of both messenger RNA (mRNA) and protein encoding the polymorphic mucin glycoprotein, Muc‐1, under most conditions in vivo and in vitro. Although steroid hormones modulate Muc‐1 expression in vivo, it is not clear if these actions are mediated directly by steroid hormone receptors or indirectly by modulation of key intracellular signal transduction cascades. To address the latter issue, we examined the effects of a wide variety of modulators of signal transduction cascades on the expression of Muc‐1 in primary cultures of polarized mouse UEC. Transient exposure of UEC to agents that inhibit tyrosine kinases by distinct mechanisms, i.e., tyrphostin, genistein, and staurosporine, consistently and significantly reduced Muc‐1 expression. In contrast, a variety of agents that modulate protein kinase A‐ or C‐dependent pathways had little or no effect on Muc‐1. The effect of tyrphostin proved to be similar in magnitude at both the level of Muc‐1 protein and mRNA expression. Transient transfection assays of mouse UEC and a murine mammary epithelial cell line, NMuMG, with mouse Muc‐1 promoter‐CAT reporter constructs demonstrated a similar (50–60%) degree of tyrphostin inhibition. These observations suggested an action at the level of Muc‐1 gene expression. Levels of 100,000g soluble tyrosine kinase activity in mouse UEC freshly isolated from estrous stage (high‐level Muc‐1 expression) and day 4 of pregnancy (low‐level Muc‐1 expression) correlated with Muc‐1 expression. Furthermore, pretreatment of day 4 pregnant mice with the anti‐progestin, RU486, an agent previously shown to restore or maintain high levels of Muc‐1 expression, also restored soluble tyrosine kinase activity to levels similar to that observed in estrous stage mice. Collectively, these results indicate that tyrosine kinase activity is required to maintain high level Muc‐1 expression in mice. J. Cell. Physiol. 170:200–208, 1997. © 1997 Wiley‐Liss, Inc.