title: TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression.
abstract: Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Feng-Feng
authors.initials: FF
authors.lastname: Zhang
authors.affiliation: Department of Basic Medicine Science, NanYang Medical College, Nanyang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Qiu
authors.affiliation: The Department of Pathology, The Traditional Chinese Medical Hospital of Xiamen, Xiamen, Fujian, People's Republic of China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Luo
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Guo-Yong
authors.initials: GY
authors.lastname: Zhu
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Ying-Fu
authors.initials: YF
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C552057:TNFAIP8L2 protein, human; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9