PLC-γ1 在表皮生长因子受体诱导的鳞癌细胞有丝分裂中是必需的。
Phospholipase C-gamma1 is required for the epidermal growth factor receptor-induced squamous cell carcinoma cell mitogenesis.
机构信息
Endocrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California, San Francisco, CA 94121, USA.
出版信息
Biochem Biophys Res Commun. 2010 Jun 25;397(2):296-300. doi: 10.1016/j.bbrc.2010.05.103. Epub 2010 May 26.
The epidermal growth factor receptor (EGFR) is a key driver in the process of squamous cell carcinoma (SCC) cell mitogenesis. Phospholipase C-gamma1 (PLC-gamma1) is a downstream target of EGFR signaling, but the role and necessity of PLC-gamma1 in EGFR-induced cell mitogenesis remain unclear. In the present study, we report an elevated expression of PLC-gamma1 in human SCC biopsies relative to adjacent normal epidermis, and in human SCC cell lines compared to normal human keratinocytes. EGFR-induced SCC cell mitogenesis was blocked by small interfering RNA knockdown of PLC-gamma1. However, inhibition of the catalytic activity of phospholipase C had no effect on EGFR-induced SCC cell mitogenesis. In response to the EGFR ligand epidermal growth factor (EGF), PLC-gamma1 was translocated not only to the plasma membrane but also to the nucleus. These data suggest that PLC-gamma1 is required for EGFR-induced SCC cell mitogenesis and the mitogenic function of PLC-gamma1 is independent of its lipase activity.
表皮生长因子受体（EGFR）是鳞状细胞癌（SCC）细胞有丝分裂过程中的关键驱动因素。磷酯酶 C-γ1（PLC-γ1）是 EGFR 信号的下游靶标，但 PLC-γ1 在 EGFR 诱导的细胞有丝分裂中的作用和必要性尚不清楚。在本研究中，我们报告了相对于相邻正常表皮，人 SCC 活检中 PLC-γ1 的表达升高，并且在人 SCC 细胞系中相对于正常人类角质形成细胞升高。通过 PLC-γ1 的小干扰 RNA 敲低抑制了 EGFR 诱导的 SCC 细胞有丝分裂。然而，抑制磷酯酶 C 的催化活性对 EGFR 诱导的 SCC 细胞有丝分裂没有影响。响应 EGFR 配体表皮生长因子（EGF），PLC-γ1 不仅易位到质膜，而且易位到核。这些数据表明，PLC-γ1 是 EGFR 诱导的 SCC 细胞有丝分裂所必需的，并且 PLC-γ1 的有丝分裂功能独立于其脂酶活性。
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