title: Downregulation of BMP6 enhances cell proliferation and chemoresistance via activation of the ERK signaling pathway in breast cancer.
abstract: Previous studies indicate that bone morphogenetic protein (BMP) 6 is involved in breast cancer development and progression. However, the mechanism underlying the role of BMP6 in breast cancer cell proliferation, differentiation and chemoresistance remains unknown. In this study, we confirmed that BMP6 expression was downregulated in breast cancer tissues compared with the adjacent normal breast tissues. We further demonstrated that the downregulation of BMP6 was correlated with the estrogen receptor (ER) and progesterone receptor (PR) status, tumor grade and enhanced proliferation (Ki67 proliferation index). In vitro functional experiments showed that the suppression of BMP6 expression by a specific small hairpin (sh)RNA vector led to increased proliferation in the MCF7 breast cancer cell line. Furthermore, knockdown of BMP6 in MCF7 cells enhanced the chemoresistance to doxorubicin by upregulation of mdr-1/P-gp expression and activation of the ERK signaling pathway. Taken together, our data suggest that BMP6 plays a critical role in breast cancer cell aberrant proliferation and chemoresistance and may serve as a novel diagnostic biomarker or therapeutic target for breast cancer.
authors.affiliation: Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Lian
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Liu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D055418:Bone Morphogenetic Protein 6 / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D061986:MCF-7 Cells; D008875:Middle Aged; D060787:Neoplasm Grading; D034622:RNA Interference; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C525816:BMP6 protein, human; D014408:Biomarkers, Tumor; D055418:Bone Morphogenetic Protein 6; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases