Protein kinase C and its isoforms in human breast cancer cells: relationship to the invasive phenotype.
Total protein kinase C (PKC) activity and the expression of 9 isoforms were determined in the estrogen receptor (ER) positive MCF-7 human breast cancer cell line, this line transfected to overexpress either PKC-á or erbB2, and in 3 ER negative breast cancer cell lines. Relationships were sought between PKC and the expression of E-cadherin, alpha-catenin, and vimentin, and urokinase-type plasminogen activator (uPA). In general, PKC enzymic activity and the conventional isoforms PKC-alpha and -gamma were higher in the ER negative, compared with the ER positive, cell lines. Over-expression of PKC-alpha by MCF-7 cells, with ER loss, was associated with the emergence of PKC- expression and a relatively high level of PKC-gamma, features typical of cells with increased proliferation rates; there was also a loss of PKC-delta, consistent with acquisition of the metastatic phenotype. Transfection to overexpress erbB2, with ER retention and slowed growth, produced a decrease in PKC-alpha and -gamma. Vimentin was expressed by the ER negative MDA-MB-231, MDA-MB-435 and PKC-alpha-transfected MCF-7 cells; they also showed loss of E-cadherin and, apart from MDA-MB-435 cells, high levels of uPA secretion. The ER negative SKBr-3 cell line was exceptional in that it had relatively low total PKC activity, low PKC-alpha and -gamma expression and no emergence of vimentin despite loss of E-cadherin expression. Compared with the other two ER negative cell lines, both the SKBr-3 and MDA-MB-435 cells had low PKC activity and uPA secretion. These results are consistent with the involvement of PKC, and notably the conventional isoforms, in the development of the metastatic phenotype, and specifically with the loss of E-cadherin and acquisition of vimentin expression, and the enhanced production of uPA.
Morse-Gaudio
M
M
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, NY 10595, USA.
Connolly
J M
JM
Rose
D P
DP
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014746:Vimentin / Q000096:biosynthesis; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D007527:Isoenzymes; D014746:Vimentin; D051178:alpha Catenin; D011493:Protein Kinase C; D014568:Urokinase-Type Plasminogen Activator