Introduction/Background Phosphatidylinositol-3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) is a PTEN inhibitor that also activates Rac 1. No associations with P-REX2a and human endometrial cancers have been reported to date.

Methodology We immunohistochemically analyzed 155 uterine endometrial malignancies for P-REX2a expression.we transduced either P-REX2a expression vector or short hairpin RNAs targeting P-REX2a into 2 uterine endometrioid carcinoma cell lines, OMC-2 and JHUEM-14.we performed expression microarray analysis using these cells, and pathway analysis.

Results The P-REX2a-positive tumors displayed worse prognosis independent of PTEN expression. Then, Ectopic expression of P-REX2a led to increased cell proliferation only in the PTEN-expressing OMC-2 cells but did not show any change in the PTEN-negative JHUEM-14 cells or the P-REX2a-knockdown cells. Induction of P-REX2a increased and knockdown of P-REX2a decreased cell migration in both cell lines. Microarray analysis revealed that the expression of members of the GPCR downstream pathway displayed the most significant changes induced by the knockdown of P-REX2a.

Conclusion P-REX2a enhanced cell motility via the GPCR downstream pathway independently of PTEN leading to progression of uterine endometrioid malignancies and poor prognosis of the patients.

Disclosure Nothing to disclose.