Tags

Type your tag names separated by a space and hit enter

Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo.
J Biol Chem 2003; 278(32):29676-85JB

Abstract

The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell growth is unclear. We determined the effects of IGFBP-5 expression on the growth of human breast cancer cell lines in vivo and in vitro. Expression of IGFBP-5, both by stable transfection and adenoviral-mediated infection, was inhibitory to the growth of MDA-MB-231 and Hs578T human breast cancer cells over a 13-day period. IGFBP-5 expression resulted in a G2/M cell cycle arrest and the induction of apoptosis in both cell lines, an effect that was abrogated in the presence of the broad-spectrum caspase inhibitor, z-VAD-fmk. IGFBP-5-induced apoptosis was associated with a transcriptional increase in expression of the proapoptotic regulator bax and decrease in the anti-apoptotic bcl-2 compared with vector controls. Secreted IGFBP-5 when added exogenously to breast cancer cells was not internalized and had no effect on cell growth or apoptosis, suggesting that IGFBP-5 may elicit its inhibitory effects via a novel, intracrine mechanism. In athymic nude mice, stable expression of IGFBP-5 significantly inhibited both the formation and growth of tumors derived from MDA-MB-231 cells. IGFBP-5-expressing tumors also had a significantly elevated level of bax mRNA and decreased levels of bcl-2 mRNA compared with vector tumors. These data suggest that IGFBP-5 is a potent growth inhibitor and proapoptotic agent in human breast cancer cells via modulation of cell cycle regulation and apoptotic mediators.

Authors+Show Affiliations

Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. abutt@med.usyd.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12777377

Citation

Butt, Alison J., et al. "Insulin-like Growth Factor-binding Protein-5 Inhibits the Growth of Human Breast Cancer Cells in Vitro and in Vivo." The Journal of Biological Chemistry, vol. 278, no. 32, 2003, pp. 29676-85.
Butt AJ, Dickson KA, McDougall F, et al. Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo. J Biol Chem. 2003;278(32):29676-85.
Butt, A. J., Dickson, K. A., McDougall, F., & Baxter, R. C. (2003). Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo. The Journal of Biological Chemistry, 278(32), pp. 29676-85.
Butt AJ, et al. Insulin-like Growth Factor-binding Protein-5 Inhibits the Growth of Human Breast Cancer Cells in Vitro and in Vivo. J Biol Chem. 2003 Aug 8;278(32):29676-85. PubMed PMID: 12777377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo. AU - Butt,Alison J, AU - Dickson,Kristie A, AU - McDougall,Fiona, AU - Baxter,Robert C, Y1 - 2003/05/30/ PY - 2003/6/5/pubmed PY - 2003/9/25/medline PY - 2003/6/5/entrez SP - 29676 EP - 85 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 278 IS - 32 N2 - The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell growth is unclear. We determined the effects of IGFBP-5 expression on the growth of human breast cancer cell lines in vivo and in vitro. Expression of IGFBP-5, both by stable transfection and adenoviral-mediated infection, was inhibitory to the growth of MDA-MB-231 and Hs578T human breast cancer cells over a 13-day period. IGFBP-5 expression resulted in a G2/M cell cycle arrest and the induction of apoptosis in both cell lines, an effect that was abrogated in the presence of the broad-spectrum caspase inhibitor, z-VAD-fmk. IGFBP-5-induced apoptosis was associated with a transcriptional increase in expression of the proapoptotic regulator bax and decrease in the anti-apoptotic bcl-2 compared with vector controls. Secreted IGFBP-5 when added exogenously to breast cancer cells was not internalized and had no effect on cell growth or apoptosis, suggesting that IGFBP-5 may elicit its inhibitory effects via a novel, intracrine mechanism. In athymic nude mice, stable expression of IGFBP-5 significantly inhibited both the formation and growth of tumors derived from MDA-MB-231 cells. IGFBP-5-expressing tumors also had a significantly elevated level of bax mRNA and decreased levels of bcl-2 mRNA compared with vector tumors. These data suggest that IGFBP-5 is a potent growth inhibitor and proapoptotic agent in human breast cancer cells via modulation of cell cycle regulation and apoptotic mediators. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12777377/Insulin_like_growth_factor_binding_protein_5_inhibits_the_growth_of_human_breast_cancer_cells_in_vitro_and_in_vivo_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=12777377 DB - PRIME DP - Unbound Medicine ER -