title: BMI-1 Promotes Self-Renewal of Radio- and Temozolomide (TMZ)-Resistant Breast Cancer Cells.
abstract: Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance. Cell proliferation and sphere number were dramatically elevated, and BMI-1 was remarkably upregulated, in IRC-R cells compared to parental cells. Silencing BMI-1 by RNA interference only affected the cell proliferation of IRC-R but not parental cells, suggesting the critical role of BMI-1 in radio- and TMZ resistance. We used a xenograft mice model to elucidate that BMI-1 was necessary in tumor development by assessing tumor volume and Ki67 expression. We found that Hedgehog (Hhg) signaling exerted synergized functions together with BMI-1, implicating the importance of BMI-1 in Hhg signaling. Downregulation of BMI-1 could be an effective strategy to suppress tumor growth, which supports the potential clinical use of targeting BMI-1 in breast cancer treatment.
authors.affiliation: 1 Department of Gland Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yan
authors.affiliation: 1 Department of Gland Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1 Department of Gland Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Pengxin
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 1 Department of Gland Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: 1 Department of Gland Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 1 Department of Gland Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000066673:Cell Self Renewal; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016513:Mice, SCID; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; C069077:BMI1 protein, human; D003606:Dacarbazine; D063150:Polycomb Repressive Complex 1; D000077204:Temozolomide
keywords: B-lymphoma moloney murine leukemia virus insertion region-1 (BMI-1); Hedgehog (Hhg); breast cancer; radioresistance; temozolomide (TMZ)