Scaglione-Sewell B, Abraham C, Bissonnette M, Skarosi S F, Hart J, Davidson N O, Wali R K, Davis B H, Sitrin M, Brasitus T A
Department of Medicine, the University of Chicago, Illinois 60637, USA.
Cancer Res. 1998 Mar 1;58(5):1074-81.
Previous studies have shown that PKC-alpha protein expression is decreased in sporadic human colon cancers, as well as in colonic tumors of rats induced by chemical carcinogens. To elucidate the potential role of PKC-alpha on several phenotypic characteristics of colon cancer cells, we have transfected cDNAs for PKC-alpha in sense or antisense orientations into CaCo-2 cells, a human colonic adenocarcinoma cell line. Transfected clones were isolated that demonstrated approximately 3-fold increases (sense transfectants) and approximately 95% decreases (antisense transfectants) in PKC-alpha expression with no significant alterations in other PKC isoforms. Transfection of CaCo-2 cells with PKC-alpha in the antisense orientation resulted in enhanced proliferation and decreased differentiation, as well as in a more aggressive transformed phenotype compared with empty vector-transfected control cells. In contrast, cells transfected with PKC-alpha cDNA in the sense orientation demonstrated decreased proliferation, enhanced differentiation, and an attenuated tumor phenotype compared with these control cells. These data show that alterations in the expression of PKC-alpha induce changes in the proliferation, differentiation, and tumorigenicity of CaCo-2 cells. Furthermore, these findings indicate that loss of PKC-alpha expression in sporadic human and chemically induced colonic cancers may confer a relative growth advantage during colonic malignant transformation.
先前的研究表明，在散发性人类结肠癌以及化学致癌物诱导的大鼠结肠肿瘤中，蛋白激酶C-α（PKC-α）蛋白表达降低。为了阐明PKC-α对结肠癌细胞几种表型特征的潜在作用，我们将有义或反义方向的PKC-α cDNA转染到人结肠腺癌细胞系CaCo-2细胞中。分离出的转染克隆显示PKC-α表达增加约3倍（有义转染子）和降低约95%（反义转染子），而其他PKC亚型无明显改变。用反义方向的PKC-α转染CaCo-2细胞导致增殖增强、分化降低，与空载体转染的对照细胞相比，转化表型更具侵袭性。相反，用有义方向的PKC-α cDNA转染的细胞与这些对照细胞相比，增殖降低、分化增强，肿瘤表型减弱。这些数据表明，PKC-α表达的改变诱导了CaCo-2细胞增殖、分化和致瘤性的变化。此外，这些发现表明，散发性人类结肠癌和化学诱导的结肠癌中PKC-α表达的缺失可能在结肠恶性转化过程中赋予相对生长优势。
