Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells.

Abstract

Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P<.001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P<.001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P<.001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P<.001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.

• Authors: Justin K Tomblin, Travis B Salisbury
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 443 Issue 3 Pg. 1092-6 (Jan 17 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24380854 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• AHR protein, human
• Basic Helix-Loop-Helix Transcription Factors
• CCND1 protein, human
• IGF2 protein, human
• Receptors, Aryl Hydrocarbon
• Cyclin D1
• Insulin-Like Growth Factor II
• Cytochrome P-450 CYP1A1

Topics

• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Breast Neoplasms (metabolism, pathology)
• Cell Proliferation (drug effects)
• Cyclin D1 (genetics)
• Cytochrome P-450 CYP1A1 (genetics, metabolism)
• Female
• Gene Knockdown Techniques
• Humans
• Insulin-Like Growth Factor II (metabolism, pharmacology)
• MCF-7 Cells
• Models, Biological
• Promoter Regions, Genetic (genetics)
• Protein Binding (drug effects)
• Receptors, Aryl Hydrocarbon (metabolism)