title: Suppression of non-small cell lung cancer proliferation and tumorigenicity by DENND2D.
abstract: DENND2D was identified as being down-regulated in lung cancer using a lung cancer low-expression suppression subtractive hybridization (SSH) library. In this study, DENND2D down-regulation has been observed not only in non-small cell lung cancer (NSCLC) cell lines and lung squamous cell carcinoma (SCC) tissues, but also in immortalized human bronchial epithelial (IHBE) cell lines and precancerous lesions, indicating that the down-regulation of DENND2D may be an early event in lung cancer. The relative DNA copy number and mRNA and protein expression levels of DENND2D were determined in vitro, and they revealed a complicated regulatory network at the genomic, transcriptional and translational levels. Over-expression of DENND2D significantly suppressed the proliferation of NSCLC cells in vitro and in vivo by inducing apoptosis. These results indicate that DENND2D might function as a tumor suppressor-like gene to prevent the survival and expansion of cells with genetic damage through apoptosis mechanism, and absence of DENND2D might play a permissive role, as an early event, in tumorigenesis.
authors.affiliation: State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ling
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zheng
authors.forename: Guobin
authors.initials: G
authors.lastname: Fu
authors.forename: Jingsong
authors.initials: J
authors.lastname: Yuan
authors.forename: Taiping
authors.initials: T
authors.lastname: Shi
authors.forename: Shiping
authors.initials: S
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.forename: Shan
authors.initials: S
authors.lastname: Zheng
authors.forename: Suping
authors.initials: S
authors.lastname: Guo
authors.forename: Naijun
authors.initials: N
authors.lastname: Han
authors.forename: Yanning
authors.initials: Y
authors.lastname: Gao
authors.forename: Shujun
authors.initials: S
authors.lastname: Cheng
authors.forename: Kaitai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C582173:DENND2D protein, human; D020662:Guanine Nucleotide Exchange Factors; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins