P2-118: Five-bromodeoxyuridine induces differentiation of a human small cell lung cancer cell line is associated with alteration of gene expression

Abstract

Small cell lung carcinoma (SCLC) is a highly metastatic disease with a poor prognosis due to its resistance to current modes of therapy. 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 established a differentiation cell model by modification of a SCLC cell line H526 with a differentiation inducing agent 5-bromodeoxyuridine (BrdU). The BrdU treatment led to a dramatic conversion from a suspension cell line H526 to an adherent cell line variant H526B exhibiting an epithelioid phenotype. DNA fingerprinting by random amplified polymorphic DNA (RAPD) method showed an identical DNA binding pattern between H526 and H526B, indicating that the H526B subpopulation arose from the original cell line H526 and the contamination from other cell types can be ruled out. The BrdU modified cells H526B remarkably reduced the ability of colony formation in soft agar and suppressed the tumor growth rate in immune-deficient nude mice. The phenotypic transition was consistent with upregulation of several lung cancer differentiation markers such as 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 like 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.