H D Kato1, H Kondoh, T Inoue, K Asanoma, T Matsuda, T Arima, K Kato, T Yoshikawa, N Wake. 1. Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyushu University, Beppu City, Oita 874-0838, Japan. hidekato@tsurumi.beppu.kyushu-u.ac.jp <hidekato@tsurumi.beppu.kyushu-u.ac.jp>
Abstract
OBJECTIVE: Although DCC has been considered as a candidate tumor suppressor, the roles it plays in the uterine endometrium and in the carcinogenic process remains unclear. To define these roles more clearly, we examined the expression of DCC and its ligand, netrin-1, in the normal endometrium and in endometrial cancer. METHODS: The expression of DCC and netrin-1 in normal endometrial glands and in cancer cell lines was examined by RT-PCR and immunohistochemistry. The effects of exogenous DCC and netrin-1 expression were observed together with the respective expression vector transfection. RESULTS: Endometrial glands in the proliferative and early secretory phase expressed both DCC and netrin-1, but glands in the late-secretory phase tended to silence DCC expression. In addition, all of the endometrial cancer cell lines lost normal DCC expression. Restored DCC expression in the cancer cell lines in the absence of netrin-1 induced apoptosis. However, no changes were observed in the presence of netrin-1. CONCLUSION: Our observations suggest that DCC/netrin-1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase. In addition, the silencing of DCC expression may contribute to the escape of endometrial cancer cells from a DCC-regulated apoptotic program, thereby promoting malignant phenotypes.
OBJECTIVE: Although DCC has been considered as a candidate tumor suppressor, the roles it plays in the uterine endometrium and in the carcinogenic process remains unclear. To define these roles more clearly, we examined the expression of DCC and its ligand, netrin-1, in the normal endometrium and in endometrial cancer. METHODS: The expression of DCC and netrin-1 in normal endometrial glands and in cancer cell lines was examined by RT-PCR and immunohistochemistry. The effects of exogenous DCC and netrin-1 expression were observed together with the respective expression vector transfection. RESULTS: Endometrial glands in the proliferative and early secretory phase expressed both DCC and netrin-1, but glands in the late-secretory phase tended to silence DCC expression. In addition, all of the endometrial cancer cell lines lost normal DCC expression. Restored DCC expression in the cancer cell lines in the absence of netrin-1 induced apoptosis. However, no changes were observed in the presence of netrin-1. CONCLUSION: Our observations suggest that DCC/netrin-1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase. In addition, the silencing of DCC expression may contribute to the escape of endometrial cancer cells from a DCC-regulated apoptotic program, thereby promoting malignant phenotypes.
Authors: Yasmin M Vasquez; San-Pin Wu; Matthew L Anderson; Shannon M Hawkins; Chad J Creighton; Madhumita Ray; Sophia Y Tsai; Ming-Jer Tsai; John P Lydon; Francesco J DeMayo Journal: Mol Endocrinol Date: 2016-03-28
Authors: Allison Jones; Andrew E Teschendorff; Quanxi Li; Jane D Hayward; Athilakshmi Kannan; Tim Mould; James West; Michal Zikan; David Cibula; Heidi Fiegl; Shih-Han Lee; Elisabeth Wik; Richard Hadwin; Rupali Arora; Charlotte Lemech; Henna Turunen; Päivi Pakarinen; Ian J Jacobs; Helga B Salvesen; Milan K Bagchi; Indrani C Bagchi; Martin Widschwendter Journal: PLoS Med Date: 2013-11-12 Impact factor: 11.069