Expression of P-REX2a is associated with poor prognosis in endometrial malignancies.

Autor:	Takeshita S; Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Yamashita Y; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Shiomi K; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Suzuki N; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Yoshida J; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Naiki-Ito A; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Suzuki S; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Akatsuka S; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, 466-8550, Japan., Toyokuni S; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, 466-8550, Japan., Takahashi T; Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, 466-8550, Japan., Mase S; Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Arakawa A; Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Sugiura-Ogasawara M; Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Takahashi S; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 May 15; Vol. 9 (37), pp. 24778-24786. Date of Electronic Publication: 2018 May 15 (Print Publication: 2018).
DOI:	10.18632/oncotarget.25349
Abstrakt:	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. In this study, we immunohistochemically analyzed 155 uterine endometrial malignancies for P-REX2a expression. The P-REX2a-positive tumors displayed worse prognosis independent of PTEN expression. Then, 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. 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. Then, we performed expression microarray analysis using these cells, and pathway analysis revealed that the expression of members of the GPCR downstream pathway displayed the most significant changes induced by the knockdown of P-REX2a. Immunohistochemical analysis revealed that Vav1, a member of the GPCR downstream pathway, was expressed in 139 of the 155 endometrial tumors, and the expression levels of Vav1 and P-REX2a showed a positive correlation ( r = 0.44, p < 0.001). In 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. Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to be declared.
Databáze:	MEDLINE
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