DECREASE IN P53 PROTEIN IN CULTURED CARDINAL LIGAMENT FIBROBLASTS FROM PATIENTS WITH PROLAPSUS UTERI

Abstract

The authors examined the growth response of cardinal ligamental fibroblasts derived from patients with prolapsus uteri (HPLiF) and compared it with the response of those from control subjects (HCLiF). The growth rate during the logarithmic growth phase was not different between HPLiF and HCLiF, while the cell density at confluence (saturation density) was significantly higher in HPLiF than in HCLiF. When added alone, platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-I), and epidermal growth factor (EGF) produced minimal effects on DNA synthesis in HCLiF. The simultaneous addition of PDGF, IGF-I and EGF synergistically stimulated the DNA synthesis. In contrast, PDGF alone was able to initiate DNA synthesis in HPLiF. The combination of PDGF, IGF-I, and EGF significantly stimulated the DNA synthesis of HPLiF compared with HCLiF. p53 protein and p53 gene transcripts decreased by 50% in HPLiF. The anti-WAF1 antibody reacted intensely with a 21-kDa protein in the homogenates of control fibroblasts, while the immunoreactive band in prolapsus fibroblasts was clearly reduced. These results indicate that the higher proliferative activity at near confluency in prolapsus fibroblasts may result from the decreased expression of p53 protein and p53 mRNA followed by the decrease in p21 protein. Furthermore, the failure of cells to enter quiescence may lead to a decrease in the synthesis and deposition of elastin and thus may contribute to the loss of supportive function in uterine connective tissues.