Expression of antisense fibronectin RNA in human colon carcinoma cells disrupts the regulation of carcinoembryonic antigen by transforming growth factor β1

Transforming growth factor β1 regulates the expression of extracellular matrix adhesion molecules and the carcinoembryonic antigen gene family of glycoproteins in the Moser colon carcinoma cell line. Expression of fibronectin antisense RNA in the Moser cells down-regulated fibronectin mRNA expression and blocked the ability of transforming growth factor β1 to stimulate fibronectin secretion. Cells expressing antisense fibronectin RNA exhibited a higher rate of proliferation, changed their morphology, and produced more laminin in response to treatment with transforming growth factor β1. The stimulation of carcinoembryonic antigen secretion by transforming growth factor β1 (which normally lagged 10-16 h behind that of fibronectin secretion stimulated by transforming growth factor β1) was blocked by the expression of antisense fibronectin RNA. Thus, the stimulation of fibronectin secretion by transforming growth factor β1 was a prerequisite for subsequent stimulation of carcinoembryonic antigen secretion. In addition, the stimulation of the cellular expression of carcinoembryonic antigen and three carcinoembryonic antigen cross-reactive species of glycoproteins by transforming growth factor β1 was down-modulated in cells expressing antisense fibronectin RNA. We therefore conclude that fibronectin may play an important role in the mechanisms of transforming growth factor β1 regulation of the expression of carcinoembryonic antigen gene family of glycoproteins.