title: DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells.
abstract: Previous studies have showed the anticancer effect of the all-trans retinoic acid (ATRA) in many tumors including breast cancer; however, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that ATRA treatment inhibited MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown. In addition, the genetic silence of DOK1 can inhibit PPARγ expression and its activity. Moreover, inactivation of PPARγ by its specific inhibitor GW9662 reversed the impacts of ATRA on cell proliferation and apoptosis. Taken together, these results indicate that ATRA-enhanced expression of DOK1 activates PPARγ leading to inhibition of cell proliferation and enhancement of cell apoptosis in MCF-7 cell.
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China. Electronic address: yaofengrmh@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D047495:PPAR gamma / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; D047495:PPAR gamma; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014212:Tretinoin
keywords: All-trans retinoic acid; Apoptosis; Breast cancer cells; Docking protein 1; Peroxisome proliferator activated receptor gamma; Proliferation