Phospholipase C-gamma1 is required for the epidermal growth factor receptor-induced squamous cell carcinoma cell mitogenesis.
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.
Endocrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California, San Francisco, CA 94121, USA. Zhongjian.Xie@gmail.com
Zhongjian
Z
Xie
Ying
Y
Chen
Er-Yuan
EY
Liao
Yi
Y
Jiang
Fu-You
FY
Liu
Sally D
SD
Pennypacker
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology; D008938:Mitosis; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051966:Phospholipase C gamma