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.
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Authors | N Sueoka, H Y Lee, S Wiehle, R J Cristiano, B Fang, L Ji, J A Roth, W K Hong, P Cohen, J M Kurie |
Journal | Oncogene
(Oncogene)
Vol. 19
Issue 38
Pg. 4432-6
(Sep 07 2000)
ISSN: 0950-9232 [Print] England |
PMID | 10980619
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Insulin-Like Growth Factor Binding Protein 6
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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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