Elevated content of the tyrosine kinase substrate phospholipase C-yl in primary human breast carcinomas
Elevated content of the tyrosine kinase substrate phospholipase C-yl in primary human breast carcinomas
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原发性人乳腺癌中酪氨酸激酶底物磷脂酶 C-yl 含量升高
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通讯作者：
G. Carpenter
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作者：
C. Arteaga;Mahlon D. Johnson;G. Todderud;R. Coffey;G. Carpenter
磷脂酶C-yl（PLC-yl）是几种受体酪氨酸激酶的底物，并且其催化活性通过酪氨酸磷酸化而增加。然而，该分子在正常或恶性人类上皮细胞增殖中的生物学意义尚不清楚。我们测定了原发性人乳腺癌和非恶性乳腺组织中PLC-yl的相对含量。通过Western印迹和免疫组化，与正常乳腺组织相比，在大多数癌和两个良性纤维腺瘤中的一个中可检测到相当高水平的PLC-γ 1蛋白。在21个癌中的18个癌中含有高水平的PLC-γ 1，也可以检测到PLC-γ 1上磷酸酪氨酸的存在。所有存在酪氨酸磷酸化PLC-y1的癌细胞也表达可检测水平的表皮生长因子受体或erbB-2，这两种酪氨酸激酶已知磷酸化这种酶。因此，高百分比的乳腺癌伴随显示受体酪氨酸激酶和直接酪氨酸磷酸化底物水平增加，从而潜在地放大信号转导途径中的两个连续步骤。
Phospholipase C-yl (PLC-yl) is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. However, the biological significance of this molecule in normal or malignant human epithelial cell proliferation is unknown. We determined the relative content of PLC-yl in primary human mammary carcinomas and in nonmalignant mammary tissues. By Western blot and immunohistochemistry, considerably higher levels of PLC-yl protein were detectable in the majority of carcinomas and in one of two benign fibroadenomas compared to normal breast tissues. In 18 of 21 carcinomas that contained high levels of PLC-y1, the presence of phosphotyrosine on PLC-yl could also be detected. All carcinomas in which tyrosine phosphorylated PLC-y1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB-2, two tyrosine kinases known to phosphorylate this enzyme. Thus, a high percentage of mammary carcinomas concomitantly display increased levels of receptor tyrosine kinases and a direct tyrosine phosphorylation substrate, thereby potentially amplifying two successive steps in a signal transduction pathway.