Elevated levels of p66 Shc are found in breast cancer cell lines and primary tumors with high metastatic potential.
Elevated levels of p66 Shc are found in breast cancer cell lines and primary tumors with high metastatic potential.
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发表时间：
2000-03
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通讯作者：
James G. Jackson;Toshiyuki Yoneda;Gary M. Clark;Douglas Yee
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作者：
James G. Jackson;Toshiyuki Yoneda;Gary M. Clark;Douglas Yee
衔接子分子Shc与转移的特定步骤有关。在目前的研究中，我们表明，在人乳腺癌细胞系MDA-MB-231的高转移性变体（F-11）中，p66 Shc亚型的表达和活化增加，而p46和p52 Shc亚型则没有变化。尽管有报道称p66 Shc可以负调控表皮生长因子信号传导至促分裂原活化蛋白激酶途径，但我们发现F-11细胞系中表皮生长因子刺激的促分裂原活化蛋白激酶活化没有变化。我们通过免疫印迹法测定了原发性乳腺癌标本中Shc的表达水平，这些标本来自有或没有腋窝淋巴结受累的患者。与淋巴结阴性标本相比，淋巴结阳性患者肿瘤中p66 Shc表达增加（斯皮尔曼相关系数= 0.43377; P = 0.0058）。此外，p66 Shc水平的增加与阳性淋巴结数量的增加相关（P = 0.032）。这项研究表明，p66 Shc的表达增加，在培养的乳腺癌细胞选择转移和原发性人乳腺癌标本中获得的患者淋巴结受累，这表明可能的作用Shc在人乳腺癌转移。
The adapter molecule Shc has been implicated in specific steps of metastasis. In the current study, we show that the expression and activation of the p66 Shc isoform increased in a highly metastatic variant (F-11) of the human breast cancer cell line MDA-MB-231 compared to the parent cell line, whereas the p46 and p52 Shc isoforms were unchanged. Despite reports that p66 Shc can negatively regulate epidermal growth factor signaling to the mitogen-activated protein kinase pathway, we found no change in epidermal growth factor-stimulated activation of mitogen-activated protein kinase in the F-11 cell line. We determined the level of Shc expression by immunoblot in primary breast cancer specimens obtained from patients with or without axillary node involvement. p66 Shc expression increased in tumors obtained from node-positive patients (Spearman correlation coefficient = 0.43377; P = 0.0058) compared to the node-negative specimens. Furthermore, increasing levels of p66 Shc correlated with an increasing number of positive nodes (P = 0.032). This study shows that p66 Shc expression increased in cultured breast cancer cells selected for metastasis and in primary human breast cancer specimens obtained from patients with lymph node involvement, suggesting a possible role for Shc in human breast cancer metastasis.