Role of epidermal growth factor in pathogenesis of uterine leiomyomas.

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.