Chakrabarty S, Huang S
Division of Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Cell Physiol. 1995 Jul;164(1):148-53. doi: 10.1002/jcp.1041640119.
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.
先前的研究表明,转化生长因子β1(TGFβ1)通过与蛋白激酶C(PKC)相关的信号转导途径调节人结肠癌细胞中癌胚抗原(CEA)和CEA交叉反应糖蛋白(CEA-GLYs)的表达(Chakrabarty,《细胞生理学杂志》,1992年,152:494 - 499)。在本研究中,我们确定了PKCα亚型在TGFβ1调节CEA和CEA-GLYs表达中的作用。通过用反义PKCα表达载体进行转染实验,PKCα反义RNA的表达导致PKCα RNA和蛋白表达的下调。在PKCα蛋白表达大幅降低的细胞中,TGFβ1无法刺激CEA的表达和分泌。然而,TGFβ1刺激95 kDa和55 kDa CEA-GLYs表达的能力未受影响。因此,我们得出结论,TGFβ1通过与PKCα相关的信号转导途径调节CEA的分泌和表达。TGFβ1也可能通过与其他PKC亚型相关的信号转导途径调节CEA-GLYs的表达。