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Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells.

Abstract
Insulin-like growth factor binding proteins (IGFBPs) are secreted into the extra-cellular matrix and inhibit cell growth through IGF-dependent and -independent mechanisms. In this study, we investigated the role of IGFBP-6, a relatively unexplored member of the IGFBP family, in the proliferation of non-small cell lung cancer (NSCLC) cells. Infection of NSCLC cell lines in vitro with an adenovirus expressing human IGFBP-6 under the control of a CMV promoter (Ad5CMV-BP6) reduced NSCLC cell number through activation of programmed cell death, as shown by cell staining with Hoechst 33342 or DNA end-labeling with bromodeoxyuridine triphosphate. The growth regulatory effect of IGFBP-6 was investigated in vivo by intratumoral injection of Ad5CMV-BP6 in NSCLC xenografts established in nu/nu mice. A single injection of Ad5CMV-BP6 reduced the size of NSCLC xenografts by 45%. These findings indicate that IGFBP-6 is a potent inducer of programmed cell death in cancer cells and support investigations into IGFBP-6 as a potential target in cancer therapeutics.
AuthorsN Sueoka, H Y Lee, S Wiehle, R J Cristiano, B Fang, L Ji, J A Roth, W K Hong, P Cohen, J M Kurie
JournalOncogene (Oncogene) Vol. 19 Issue 38 Pg. 4432-6 (Sep 07 2000) ISSN: 0950-9232 [Print] England
PMID10980619 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Insulin-Like Growth Factor Binding Protein 6
Topics
  • Adenoviridae (genetics)
  • Animals
  • Apoptosis (physiology)
  • Carcinogenicity Tests
  • Carcinoma, Non-Small-Cell Lung (metabolism, pathology, virology)
  • Cell Division
  • DNA Fragmentation
  • Humans
  • Insulin-Like Growth Factor Binding Protein 6 (genetics, metabolism)
  • Lung Neoplasms (metabolism, pathology, virology)
  • Mice
  • Mice, Nude
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

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