Tags

Type your tag names separated by a space and hit enter

Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells.
J Biol Chem 2000; 275(50):39174-81JB

Abstract

We report that transfection of insulin-like growth factor-binding protein-3 (IGFBP-3) cDNA in human breast cancer cell lines expressing either mutant p53 (T47D) or wild-type p53 (MCF-7) induces apoptosis. IGFBP-3 also increases the ratio of pro-apoptotic to anti-apoptotic members of the Bcl-2 family. In MCF-7, an increase in Bad and Bax protein expression and a decrease in Bcl-x(L) protein and Bcl-2 protein and mRNA were observed. In T47D, Bax and Bad proteins were up-regulated; Bcl-2 protein is undetectable in these cells. As T47D expresses mutant p53 protein, these modulations of pro-apoptotic proteins and induction of apoptosis are independent of p53. The effect of IGFBP-3 on the response of T47D to ionizing radiation (IR) was examined. These cells do not G(1) arrest in response to IR and are relatively radioresistant. Transfection of IGFBP-3 increased the radiosensitivity of T47D and increased IR-induced apoptosis but did not effect a rapid G(1) arrest. IR also caused a much greater increase in Bax protein in IGFBP-3 transfectants compared with vector controls. Thus, IGFBP-3 increases the expression of pro-apoptotic proteins and apoptosis both basally and in response to IR, suggesting it may be a p53-independent effector of apoptosis in breast cancer cells via its modulation of the Bax:Bcl-2 protein ratio.

Authors+Show Affiliations

Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, 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

10998426

Citation

Butt, A J., et al. "Insulin-like Growth Factor-binding Protein-3 Modulates Expression of Bax and Bcl-2 and Potentiates P53-independent Radiation-induced Apoptosis in Human Breast Cancer Cells." The Journal of Biological Chemistry, vol. 275, no. 50, 2000, pp. 39174-81.
Butt AJ, Firth SM, King MA, et al. Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. J Biol Chem. 2000;275(50):39174-81.
Butt, A. J., Firth, S. M., King, M. A., & Baxter, R. C. (2000). Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. The Journal of Biological Chemistry, 275(50), pp. 39174-81.
Butt AJ, et al. Insulin-like Growth Factor-binding Protein-3 Modulates Expression of Bax and Bcl-2 and Potentiates P53-independent Radiation-induced Apoptosis in Human Breast Cancer Cells. J Biol Chem. 2000 Dec 15;275(50):39174-81. PubMed PMID: 10998426.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. AU - Butt,A J, AU - Firth,S M, AU - King,M A, AU - Baxter,R C, PY - 2000/9/22/pubmed PY - 2001/3/3/medline PY - 2000/9/22/entrez SP - 39174 EP - 81 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 275 IS - 50 N2 - We report that transfection of insulin-like growth factor-binding protein-3 (IGFBP-3) cDNA in human breast cancer cell lines expressing either mutant p53 (T47D) or wild-type p53 (MCF-7) induces apoptosis. IGFBP-3 also increases the ratio of pro-apoptotic to anti-apoptotic members of the Bcl-2 family. In MCF-7, an increase in Bad and Bax protein expression and a decrease in Bcl-x(L) protein and Bcl-2 protein and mRNA were observed. In T47D, Bax and Bad proteins were up-regulated; Bcl-2 protein is undetectable in these cells. As T47D expresses mutant p53 protein, these modulations of pro-apoptotic proteins and induction of apoptosis are independent of p53. The effect of IGFBP-3 on the response of T47D to ionizing radiation (IR) was examined. These cells do not G(1) arrest in response to IR and are relatively radioresistant. Transfection of IGFBP-3 increased the radiosensitivity of T47D and increased IR-induced apoptosis but did not effect a rapid G(1) arrest. IR also caused a much greater increase in Bax protein in IGFBP-3 transfectants compared with vector controls. Thus, IGFBP-3 increases the expression of pro-apoptotic proteins and apoptosis both basally and in response to IR, suggesting it may be a p53-independent effector of apoptosis in breast cancer cells via its modulation of the Bax:Bcl-2 protein ratio. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/10998426/Insulin_like_growth_factor_binding_protein_3_modulates_expression_of_Bax_and_Bcl_2_and_potentiates_p53_independent_radiation_induced_apoptosis_in_human_breast_cancer_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=10998426 DB - PRIME DP - Unbound Medicine ER -