EXPRESSION OF ANTISENSE FIBRONECTIN RNA IN HUMAN COLON-CARCINOMA CELLS DISRUPTS THE REGULATION OF CARCINOEMBRYONIC ANTIGEN BY TRANSFORMING GROWTH-FACTOR-BETA-1

Transforming growth factor beta 1 regulates the expression of extracel lular matrix adhesion molecules and the carcinoembryonic antigen gene family of glycoproteins in the Moser colon carcinoma cell line. Expres sion of fibronectin antisense RNA in the Moser cells down-regulated fi bronectin mRNA expression and blocked the ability of transforming grow th factor beta 1 to stimulate fibronectin secretion. Cells expressing antisense fibronectin RNA exhibited a higher rate of proliferation, ch anged their morphology, and produced more laminin in response to treat ment with transforming growth factor beta 1. The stimulation of carcin oembryonic antigen secretion by transforming growth factor beta 1 (whi ch normally lagged 10-16 h behind that of fibronectin secretion stimul ated by transforming growth factor beta 1) was blocked by the expressi on of antisense fibronectin RNA. Thus, the stimulation of fibronectin secretion by transforming growth factor beta 1 was a prerequisite for subsequent stimulation of carcinoembryonic antigen secretion. In addit ion, the stimulation of the cellular expression of carcinoembryonic an tigen and three carcinoembryonic antigen cross-reactive species of gly co proteins by transforming growth factor beta 1 was downmodulated in cells expressing antisense fibronectin RNA. We therefore conclude that fibronectin may play an important role in the mechanisms of transform ing growth factor beta 1 regulation of the expression of carcinoembryo nic antigen gene family of glycoproteins.