Protein kinase C and its isoforms in human breast cancer cells: relationship to the invasive phenotype.
Protein kinase C and its isoforms in human breast cancer cells: relationship to the invasive phenotype.
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DOI：
10.3892/ijo.12.6.1349
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发表时间：
1998-06
影响因子：
5.2
通讯作者：
M. Morse-Gaudio;J. Connolly;D. Rose
中科院分区：
文献类型：
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作者：
M. Morse-Gaudio;J. Connolly;D. Rose
在雌激素受体（ER）阳性的MCF-7人乳腺癌细胞系中，通过转染PKC- <e:1>或erbB2过表达，以及在3个ER阴性的乳腺癌细胞系中，测定了总蛋白激酶C （PKC）活性和9种亚型的表达。寻找PKC与E-cadherin、α -catenin、vimentin和尿激酶型纤溶酶原激活物（uPA）表达之间的关系。总的来说，与ER阳性细胞系相比，ER阴性细胞系的PKC酶活性以及PKC- α和- γ的常规同工型更高。MCF-7细胞过度表达PKC- α并伴有内质网缺失，与PKC-表达和相对高水平PKC- γ的出现有关，这是增殖率增加的细胞的典型特征；pkc - δ的缺失也与转移表型的获得一致。转染过表达erbB2，内质网保留和生长减慢，产生pkc - α和- γ的减少。在ER阴性的MDA-MB-231、MDA-MB-435和pkc - α转染的MCF-7细胞中表达Vimentin；它们也表现出e -钙粘蛋白的缺失，除了MDA-MB-435细胞外，uPA分泌水平也很高。ER阴性SKBr-3细胞系的特殊之处在于，它的总PKC活性相对较低，PKC- α和- γ表达较低，尽管E-cadherin表达缺失，但没有出现波形蛋白。与其他两种ER阴性细胞系相比，SKBr-3和MDA-MB-435细胞的PKC活性和uPA分泌均较低。这些结果与PKC的参与一致，特别是传统的同种异构体，在转移表型的发展中，特别是与E-cadherin的缺失和vimentin表达的获得，以及uPA的增强产生一致。
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.