Volume 12 Supplement 1

Breast Cancer Research 2010

Open Access

Insulin-like growth factor binding protein-2 alters the sensitivity of breast cancer cells to chemotherapy

  • EJ Foulstone1,
  • JM Holly1,
  • L Zeng1,
  • ZE Winters1 and
  • CM Perks1
Breast Cancer Research201012(Suppl 1):P22

DOI: 10.1186/bcr2519

Published: 18 May 2010

Introduction

Insulin-like growth factor binding protein-2 (IGFBP-2) is often elevated in breast tumours and the presence of IGFBP-2 has been shown to correlate with malignancy. Previously we have shown that IGFBP-2 reduces PTEN abundance [1] and thus helps to maintain the activity of the phosphoinositide 3-kinase signalling cascade, a key mitogenic and survival pathway.

Objective

We therefore investigated whether IGFBP-2 could act as a survival factor for breast cancer cell lines. Using MCF7 and T47D cells, we tested the ability of exogenous IGFBP-2 to alter apoptosis induced by various chemotherapeutic agents. As both these cell lines produce large amounts of IGFBP-2, we also examined the effect of silencing IGFBP-2 using siRNA.

Results

In MCF7 cells, paclitaxel (50 μM) increased cell death from 9% to 24.5% (P < 0.001). Addition of IGFBP-2 (25 ng/ml) decreased the induced cell death by almost one-half to 17.7% (P = 0.047). 5-Fluorouricil (20 μM) increased cell death of T47D cells by 54% (P = 0.044), which was completely blocked by the addition of IGFBP-2. Conversely, loss of IGFBP-2 enhanced chemotherapy-induced apoptosis in both cell lines compared with a nonsilencing siRNA. We also observed that loss of IGFBP-2 reduced cellular proliferation - the live cell number decreased 73% (P < 0.001) and 33% (P < 0.001) in the MCF7 and T47D cells, respectively. Additionally, in the MCF7 cells, loss of IGFBP-2 alone increased cell death threefold (P < 0.001).

Conclusions

These data show that the production of IGFBP-2 by breast cancer cells enhances their survival and protects them against chemotherapy. Thus in breast tumours the increase in IGFBP-2 production could be a survival mechanism making IGFBP-2 a legitimate target for intervention.

Declarations

Acknowledgements

This research was funded by Breast Cancer Campaign.

Authors’ Affiliations

(1)
University of Bristol

References

  1. Perks CM, Vernon EG, Rosenthal AH, Tonge D, Holly JM: IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells. Oncogene. 2007, 26: 5966-5972. 10.1038/sj.onc.1210397.PubMedView ArticleGoogle Scholar

Copyright

© BioMed Central Ltd. 2010

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