Endocrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California, San Francisco, CA 94121, USA.
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。
