Hui-Chen Wang1,2, Yen-Nien Huo1, Wen-Sen Lee3,4,5,6. 1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. 2. Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. 3. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. wslee@tmu.edu.tw. 4. Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. wslee@tmu.edu.tw. 5. Cancer Research Center, Taipei Medical University Hospital, Taipei, 110, Taiwan. wslee@tmu.edu.tw. 6. Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. wslee@tmu.edu.tw.
Abstract
PURPOSE: We previously demonstrated that progesterone (P4) interacted with folic acid (FA) and abolished the FA-reduced endothelial cell proliferation and migration. These findings led us to investigate whether FA can interfere with the P4-promoted breast cancer cell proliferation and migration. METHODS: We conducted MTT and wound healing assay to evaluate cell proliferation and migration, respectively. Western blot analysis and immunoprecipitation were performed to examine the protein expression and protein-protein interaction, respectively. RESULTS: We demonstrated that P4 promoted proliferation and migration of breast cancer cell lines (T47D, MCF-7, BT474, and BT483). However, co-treatment with P4 and FA together abolished these promotion effects. Treatment with P4 alone increased the formation of PR-cSrc complex and the phosphorylation of cSrc at tyrosine 416 (Tyr416). However, co-treatment with P4 and FA together increased the formations of cSrc-p140Cap, cSrc-Csk, and cSrc-p-Csk complex, and the phosphorylation of cSrc at tyrosine 527 (Tyr527). Co-treatment with P4 and FA together also abolished the activation of cSrc-mediated signaling pathways involved in the P4-promoted breast cancer cell proliferation and migration. CONCLUSIONS: Co-treatment with FA and P4 together abolished the P4-promoted breast cancer cell proliferation and migration through decreasing the formation of PR-cSrc complex and increasing the formations of cSrc-p140Cap and cSrc-Csk complex, subsequently activating Csk, which in turn suppressed the phosphorylation of cSrc at Tyr416 and increased the phosphorylation of cSrc at Tyr527, hence inactivating the cSrc-mediated signaling pathways. The findings from this study might provide a new strategy for preventing the P4-promoted breast cancer progress.
PURPOSE: We previously demonstrated that progesterone (P4) interacted with folic acid (FA) and abolished the FA-reduced endothelial cell proliferation and migration. These findings led us to investigate whether FA can interfere with the P4-promoted breast cancer cell proliferation and migration. METHODS: We conducted MTT and wound healing assay to evaluate cell proliferation and migration, respectively. Western blot analysis and immunoprecipitation were performed to examine the protein expression and protein-protein interaction, respectively. RESULTS: We demonstrated that P4 promoted proliferation and migration of breast cancer cell lines (T47D, MCF-7, BT474, and BT483). However, co-treatment with P4 and FA together abolished these promotion effects. Treatment with P4 alone increased the formation of PR-cSrc complex and the phosphorylation of cSrc at tyrosine 416 (Tyr416). However, co-treatment with P4 and FA together increased the formations of cSrc-p140Cap, cSrc-Csk, and cSrc-p-Csk complex, and the phosphorylation of cSrc at tyrosine 527 (Tyr527). Co-treatment with P4 and FA together also abolished the activation of cSrc-mediated signaling pathways involved in the P4-promoted breast cancer cell proliferation and migration. CONCLUSIONS: Co-treatment with FA and P4 together abolished the P4-promoted breast cancer cell proliferation and migration through decreasing the formation of PR-cSrc complex and increasing the formations of cSrc-p140Cap and cSrc-Csk complex, subsequently activating Csk, which in turn suppressed the phosphorylation of cSrc at Tyr416 and increased the phosphorylation of cSrc at Tyr527, hence inactivating the cSrc-mediated signaling pathways. The findings from this study might provide a new strategy for preventing the P4-promoted breast cancer progress.
Authors: Viroj Boonyaratanakornkit; Eileen McGowan; Lori Sherman; Michael A Mancini; Boris J Cheskis; Dean P Edwards Journal: Mol Endocrinol Date: 2006-11-30
Authors: Garnet L Anderson; Marian Limacher; Annlouise R Assaf; Tamsen Bassford; Shirley A A Beresford; Henry Black; Denise Bonds; Robert Brunner; Robert Brzyski; Bette Caan; Rowan Chlebowski; David Curb; Margery Gass; Jennifer Hays; Gerardo Heiss; Susan Hendrix; Barbara V Howard; Judith Hsia; Allan Hubbell; Rebecca Jackson; Karen C Johnson; Howard Judd; Jane Morley Kotchen; Lewis Kuller; Andrea Z LaCroix; Dorothy Lane; Robert D Langer; Norman Lasser; Cora E Lewis; JoAnn Manson; Karen Margolis; Judith Ockene; Mary Jo O'Sullivan; Lawrence Phillips; Ross L Prentice; Cheryl Ritenbaugh; John Robbins; Jacques E Rossouw; Gloria Sarto; Marcia L Stefanick; Linda Van Horn; Jean Wactawski-Wende; Robert Wallace; Sylvia Wassertheil-Smoller Journal: JAMA Date: 2004-04-14 Impact factor: 56.272