We hypothesized that p27(kip1) overexpression can regulate
endometriosis cell proliferation, apoptosis and
vascular endothelial growth factor (
VEGF) expression in the endometrium. The overexpression of p27(kip1) was obtained by transduction of p27(kip1) in primary cultures of endometrium obtained from women with
endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27(kip1) expression in endometrial cells primary culture. The effect of p27(kip1) overexpression was elucidated through the cell proliferation evaluation and the expression of the cell cycle-related
proteins p16, p21, p27, and p53. Cell cycle and apoptosis in endometrial cells from women with and without
endometriosis were also evaluated. The
VEGF levels were evaluated 1 and 7 days after transduction. The experiments were performed using Immunofluorescence stainings and flow cytometry technique. The cell proliferation statistically diminished markedly following p27(kip1) overexpression in the
endometriosis group. This process was accompanied, however, by a statistically significant modulation of the cell cycle-related
proteins p16, p21, p27 and p53 markedly increase following p27(kip1) overexpression in the
endometriosis group (p < 0.001) and an increase in apoptotic cells was observed. In the
endometriosis group, significant downregulation of
VEGF expression was observed 7 days after p27(kip1) overexpression, attaining levels strikingly similar to those observed in the control endometrial cells. The findings of this study showed a link between the cell cycle control
protein (p27(kip1)) and angiogenesis (
VEGF). Our results, also reinforces the background of endometrial dysfunction as part of the origin of
endometriosis. We believe that better knowledge of endometrium milieu and the establishment of the link between different, previously describe, altered pathways in this tissue can facilitate future genetic
cell therapy.