title: Clinical implications of BMI-1 in cancer stem cells of laryngeal carcinoma.
abstract: The objective of this study is to investigate the chemoresistance of CD133(+) cancer stem cells in Hep-2 cells of laryngeal cancer and detect the expression mRNA and protein levels of BMI-1 in CD133(+) cells and CD133(-) cells. The response of Hep-2 cells to different chemotherapeutic agents was investigated, and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed chemotherapy resistance. Colony formation assays were studied and cells were injected subcutaneously into axillary fossa of node mice to measure the tumor-forming ability. RT-PCR and Western blot analyses were used to detect the expression levels of BMI-1 in the different subpopulation cells. It was concluded that chemotherapy enriched the CD133(+) subpopulation 2-fourfold, relative to the untreated cells. 1.55 ± 0.28% of Hep-2 cells were observed to be CD133(+) cells. Flow cytometric analysis revealed that after the treatment with these chemotherapeutic agents, the expression of CD133 was up to 5.16 ± 0.86%, 4.94 ± 0.58%, 3.66 ± 0.59%. After 5-FU treatment, the expression of CD133 was 6.7 ± 1.6% relative to the untreated mice 2.6 ± 0.96% by nude mice tumor xenograft model. CD133(+) cancer stem cells were more resistant to chemotherapy; the proliferation capability and tumor-forming ability were no difference after chemotherapy. Semi-quantitative RT-PCR and Western blot analyses provided strong evidence that BMI-1 expression in CD133(+) cells is different from CD133(-) cells remarkably. Taken together, it was confirmed that CD133(+) cancer stem cells were chemoresistant and BMI-1 was highly expressed in these CD133(+) cells.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, 130041, Jilin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jingpu
authors.initials: J
authors.lastname: Yang
authors.forename: Chunshun
authors.initials: C
authors.lastname: Jin
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.forename: Jinzhang
authors.initials: J
authors.lastname: Cheng
authors.forename: Xueshibojie
authors.initials: X
authors.lastname: Liu
authors.forename: Xinmeng
authors.initials: X
authors.lastname: Qi
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016190:Carboplatin / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C069077:BMI1 protein, human; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D063150:Polycomb Repressive Complex 1; D005472:Fluorouracil