The Role of Insulin-like Growth Factor Binding Protein (IGFBP)-2 in DNA Repair and Chemoresistance in Breast Cancer Cells

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jun 19

PMID 38893232

Authors

Alaa Mohammedali

Kalina Biernacka

Rachel M Barker

Jeff M P Holly

Claire M Perks

Affiliations

Soon will be listed here.

Abstract

The role if insulin-like growth factor binding protein-2 (IGFBP-2) in mediating chemoresistance in breast cancer cells has been demonstrated, but the mechanism of action is unclear. This study aimed to further investigate the role of IGFBP-2 in the DNA damage response induced by etoposide in MCF-7, T47D (ER+ve), and MDA-MB-231 (ER-ve) breast cancer cell lines. In the presence or absence of etoposide, IGFBP-2 was silenced using siRNA in the ER-positive cell lines, or exogenous IGFBP-2 was added to the ER-negative MDA-MB-231 cells. Cell number and death were assessed using trypan blue dye exclusion assay, changes in abundance of proteins were monitored using Western blotting of whole cell lysates, and localization and abundance were determined using immunofluorescence and cell fractionation. Results from ER-positive cell lines demonstrated that upon exposure to etoposide, loss of IGFBP-2 enhanced cell death, and this was associated with a reduction in P-DNA-PKcs and an increase in γH2AX. Conversely, with ER-negative cells, the addition of IGFBP-2 in the presence of etoposide resulted in cell survival, an increase in P-DNA-PKcs, and a reduction in γH2AX. In summary, IGFBP-2 is a survival factor for breast cancer cells that is associated with enhancement of the DNA repair mechanism.

Citing Articles

Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer.

Kotsifaki A, Maroulaki S, Karalexis E, Stathaki M, Armakolas A Int J Mol Sci. 2024; 25(17).

PMID: 39273251 PMC: 11394947. DOI: 10.3390/ijms25179302.

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