5-Bromodeoxyuridine induced differentiation of a human small cell lung cancer cell line is associated with alteration of gene expression.
Small cell lung cancer (SCLC) appears to arise from neuroendocrine cells with the potential to differentiate into a variety of lung epithelial cell lineages. In order to investigate molecular events underlying the cell type transition in SCLC, we treated a SCLC cell line H526 with a differentiation inducing agent 5-bromodeoxyuridine (BrdU). The treatment led to a dramatic conversion from suspension cells to adherent cells exhibiting an epithelioid phenotype, which remarkably reduced the ability of colony formation in soft agar and suppressed the tumor growth rate in nude mice. The phenotypic transition was consistent with upregulation of surfactant protein C (SFTPC), thyroid transcription factor 1 (TTF-1), Connexin 26 (Cx26), insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), as well as homeobox genes LAGY, PITX1, and HOXB2. Our data suggest that BrdU induced cell differentiation could be linked to the development of a less aggressively phenotype in small cell lung cancer.
Chen
Yuan
Y
Institute of Pathology, Charité Medical School, University Hospital Charité, Humboldt-University, Schumannstr 20-21, D-10098 Berlin, Germany.
Pacyna-Gengelbach
Manuela
M
Deutschmann
Nicole
N
Ye
Fei
F
Petersen
Iver
I
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D000072259:Connexin 26; D017630:Connexins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D015854:Up-Regulation
D017630:Connexins; D004268:DNA-Binding Proteins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; C086061:HOXB2 protein, human; D018398:Homeodomain Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D051761:Paired Box Transcription Factors; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human; C504003:TTF1 protein, human; D014157:Transcription Factors; C101485:homeobox protein PITX1; C102529:insulin-like growth factor binding protein-related protein 1; D000072259:Connexin 26; D001973:Bromodeoxyuridine