Role of protein kinase cα in the induction of carcinoembryonic antigen by transforming growth factor β

Abstract

Previous studies showed that transforming growth factor beta 1 (TGF beta 1) regulates the expression of carcinoembryonic antigen (CEA) and CEA-cross-reactive glycoproteins (CEA-GLYs) in human colon carcinoma cells through a signal-transducing pathway associated with protein kinase C (PKC) (Chakrabarty, J. Cell. Physiol., 1992, 152:494-499). In this study we determined the role of the PKC alpha isoform in the regulation of CEA and CEA-GLYs expression by TGF beta 1. Expression of PKC alpha antisense RNA, through transfection experiments with an antisense PKC alpha expression vector, resulted in down-modulation of PKC alpha RNA and protein expression. TGF beta 1 was unable to stimulate the expression and secretion of CEA in cells in which the expression of PKC alpha protein was substantially reduced. The ability of TGF beta 1 to stimulate the expression of the 95- and 55-kDa CEA-GLYs, however, was not affected. We therefore conclude that TGF beta 1 regulates the secretion and expression of CEA through a signal-transducing pathway associated with PKC alpha. TGF beta 1 may also regulate the expression of CEA-GLYs through signal-transducing pathways associated with other PKC isoforms.

Elevated serum levels of transforming growth factor-?1 in patients with colorectal carcinoma

“…However, some studies have reported a relation between TGF-␤1 and CEA. [27][28][29] Our results revealed a significant correlation between serum levels of TGF-␤1 and serum levels of CEA. Serum TGF-␤1 increased with increasing serum levels of CEA.…”

Ectopic Expression of eIF-4E in Human Colon Cancer Cells Promotes the Stimulation of Adhesion Molecules by Transforming Growth Factorβ

“…Protein kinase C (PKC) is a ubiquitous family of protein kinases that is involved in transmembrane signaling in cellular responses to extracellular signals (Nishizuka, 1992). We have previously shown that in Moser cells TGFP rapidly stimulates a PKC phosphotransferase activity before the stimulation of the adhesion response and that the stimulation of PKC phosphotransferase activity by TGFP is required for the adhesion response to occur (Chakrabarty, 1992b;Chakrabarty and Huang, 1995). In addition, the postreceptor TGFP-PKC signal pathway controls the adhesion but not the antiproliferative response to TGFP (Chakrabarty et al, 1998).…”

Transforming growth factor β regulates cell–cell adhesion through extracellular matrix remodeling and activation of focal adhesion kinase in human colon carcinoma Moser cells

“…Increase in cell-matrix adhesion is mediated through the induction of the synthesis and secretion of the extracellular matrix (ECM)-adhesion molecules laminin and fibronectin with a concurrent upregulation of the expression of cell-surface integrin receptors for these ECM-adhesion molecules (Huang and Chakrabarty, 1994;Chakrabarty et al, 1998), collectively termed ECM remodeling). TGFb regulates ECM remodeling in the Moser cells in a protein kinase C-dependent manner (Chakrabarty and Huang, 1995;Chakrabarty et al, 1998). Almost concurrently with ECM remodeling, TGFb induces cell-cell adhesion through the induction of E-cadherin expression (Wang and Chakrabarty, 2001), an epithelial associated homotypic cell-cell adhesion molecule known to have tumorsuppressive function in colon cancer (Breen et al, 1995).…”