title: The effect of down regulation of calcineurin Aα by lentiviral vector-mediated RNAi on the biological behavior of small-cell lung cancer and its bone metastasis.
abstract: Bone is the third most common site of cancer metastasis. Over 30 to 40% of lung cancers can develop skeletal metastasis and no effective curative therapy exists in clinic cases. Previously we screened the different expression of proteins between SBC-5 cells and SBC-3 cells by proteomic study methods (MALDI-TOF/TOF-MS) and found that calcineurin (hereafter referred as Cn) overexpresses in SBC-5 which has special priority in metastasis to bone in a multiple-organ metastasis mice model. However the roles of Cn in osteotropism of SCLC remain to be elucidated. At present study, we decrease CnAα expression in SBC-5 by lentiviral vector-mediated RNAi and found that down regulation of CnAα gene expression can decrease the proliferation and colony formation rate, impede the cell cycle progression, reduce the cell migration and invasion, and inhibit cells adhering to bone matrix, but not change the apoptosis rate of SBC-5 in vitro. In vivo down or up regulation of CnAα gene expression can only decrease or increase the bone metastasis rate, but not affect the metastasis rate to the visceral organs. Our research reveals that CnAα is closely related to the osteotropism metastasis of SCLC and a candidate tumor promotor gene for developing bone metastases.
authors.affiliation: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Ning-Qiang
authors.initials: NQ
authors.lastname: Ma
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Min
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Wang
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan-Guo
authors.initials: YG
authors.lastname: Feng
authors.forename: Hai-Chuan
authors.initials: HC
authors.lastname: Su
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Feng
authors.forename: He-Long
authors.initials: HL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D016086:Lentivirus / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D065095:Calcineurin Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019703:Calcineurin; C525673:PPP3CA protein, human