Role of epidermal growth factor in pathogenesis of uterine leiomyomas

ABSTRACT

Objective: To investigate the role of epidermal growth factor (EGF) in the pathogenesis of uterine leiomyomas. Methods: Human myometrial smooth muscle cells (HM-SMCs) and smooth muscle cells of human uterine leiomyomas (HL-SMCs) were separated from patients' specimens and cultured. After processed by EGF or PD98059 (inhibitor of MKK/MEK) +EGF, the proliferation rate of both SMCs was detected by BrdU method and the phosphorylation level of p44/42 mitogen-activated protein kinase (MAPK) was determined by Western-blot. After different processing time by EGF, the phosphorylation levels of p44/42 MAPK and AKT and p27 expression level in both SMCs were detected by Western-blot. Results: EGF could significantly promote HL-SMCs proliferation and PD98059 could inhibit this effect (P<0.05); besides, PD98059 could inhibit the increase of the phosphorylation level of p44/42 MAPK in both SMCs induced by EGF. When the processing time by EGF was over 15min, the phosphorylation levels of p44/42 MAPK and AKT in both SMCs decreased sharply and were close to zero; p27 expression in HM-SMCs raised significantly while the upregulation in HL-SMCs was little. Conclusions: EGF could not cause activation of EGFR because of the dephosphorylation of p44/42 MAPK and AKT in HL-SMCs, which caused p27 expression insufficiently and cell cycle dysregulation.