Down-regulation of p21-activated kinase 1 by progestin and its increased expression in the eutopic endometrium of women with endometriosis

Sung Hoon Kim, Kim SH, Hoi Woul Lee, Lee HW, H. W. Lee, Kim YH, Y. H. Kim, Young Hoon Kim, Yun Hee Koo, Koo YH, Y. H. Koo, Hee Dong Chae, Chae HD, Hee‐Dong Chae, Kim CH, Chung Hoon Kim, C. H. Kim, P. R. Lee, Lee PR, Pil Ryang Lee, Byung Moon Kang, B.-M. Kang, Kang BM
Human Reproduction · 2009 · vol. 24(5) , pp. 1133–1141 · doi:10.1093/humrep/den484 · PMID:19168872 · W2157107089
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Progestin treatment decreased p21-activated kinase 1 (Pak1) in endometrial cells, but Pak1 expression was increased in the eutopic endometrium of women with endometriosis, and Pak1 knockdown reduced cell viability.

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Abstract

BACKGROUND: P21-activated kinase 1 (Pak1) integrates various signaling pathways that are vital to cell survival and function. This study was performed to evaluate whether sex steroids may regulate the expression of Pak1 in endometrial cells as well as whether its expression is increased in the eutopic endometrium of women with endometriosis. METHODS: Following in vitro estradiol (E(2)) and/or medroxyprogesterone acetate (MPA) treatment of Ishikawa cells and endometrial stromal cells (ESCs), Pak1 protein was analyzed utilizing western blot analysis and immunocytochemistry. Immunohistochemistry was performed to evaluate Pak1 immunoreactivity semiquantitatively in women with endometriosis and in controls. To assess the role of Pak1 on endometrial cell viability, crystal violet assay was performed following transfection of Ishikawa cells with Pak1 small interfering RNA (siRNA). RESULTS: In vitro treatment with E(2) plus MPA or MPA alone led to a significant decrease of Pak1 protein in Ishikawa cells and ESCs (both P < 0.05 versus control). Immunohistochemistry also revealed that Pak1 protein is significantly decreased during the secretory phase in both epithelial and stromal cells in the control subjects (P < 0.001 and P < 0.01, respectively). The immunoreactivity of Pak1 in glandular cells was significantly increased in the eutopic endometrium of women with endometriosis compared with the controls during the secretory phase (P < 0.01). Crystal violet assay has shown that transfection of Ishikawa cells with Pak1 siRNA led to a significant decrease of cellular viability (P < 0.05). CONCLUSIONS: These findings suggest that Pak1 is down-regulated by progesterone during the secretory phase in normal endometrium and increased Pak1 activity during the secretory phase might lead to establishment of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Down-Regulation Endometriosis Endometrium Medroxyprogesterone Acetate p21-Activated Kinases Progestins Adult Cell Line Down-Regulation Endometriosis Endometrium Estradiol Estradiol Female Humans Immunohistochemistry Medroxyprogesterone Acetate Menstrual Cycle Menstrual Cycle p21-Activated Kinases

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