Different effects of epidermal growth factor on smooth muscle cells derived from human myometrium and from leiomyoma

Objective: To determine different effects of epidermal growth factor (EGF) on cultured smooth muscle cells (SMCs) derived from human myometrium and leiomyoma. Design: EGF effects on DNA synthesis and intracellular signal transduction were studied in cultured SMCs from leiomyoma and its matched myometrium. Setting: Research laboratories. Patient(s): Patients 35-50 years old with uterine leiomyomas. Intervention(s): Hysterectomy. Main Outcome Measure(s): Signal transduction from EGF receptor. Result(s): As analyzed by laser scanning cytometry (LSC), EGF treatment stimulated DNA synthesis and induced polyploidization of leiomyomal, but not myometrial, SMCs. EGF stimulation was inhibited by AG1478, an EGF receptor (EGFR) inhibitor and PD98059, a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor. Both leiomyomal and myometrial SMCs had similar expression levels of EGFR, but EGF treatment induced transient phosphorylation activation of EGFR and Akt in leiomyomal SMCs. Consequently, EGF triggered transient phosphorylation activation of p44/42 MAPK in leiomyomal SMCs, followed by down-regulation of p27. In myometrial SMCs, however, EGF induced sustained activation of EGFR, Akt, and p44/42 MAPK with upregulation of p27. Conclusion(s): EGF stimulates DNA synthesis and polyploidization in leiomyomal SMCs through transient activation of the EGFR-MAPK pathway. Given that polyploidization plays a role in tumorigenesis, our results shed new light on the pathogenesis of human uterine leiomyoma. (Fertil Steril (R) 2011; 96: 1015-20. (C) 2011 by American Society for Reproductive Medicine.)