Endocrine Abstracts

Context: GH and insulin-like growth factor (IGF1) play important roles in breast cancer (BC) development. IGF1 has been shown to importantly influence estrogen effects on BC, suggesting that estrogen receptors (ER) may mediate also GH effects. We previously demonstrated that GH and IGF1 protect the ER positive BC-derived MCF7 cell line towards the cytotoxic effects of doxorubicin (D), independently of IGF1.

Aim of the study: Evaluate whether this holds true also in the ER negative BC-derived MDA-MB-231 cell line and in the normal MCF-12A breast cell line. In addition, we investigated the possible mechanisms implicated in the protective action of GH towards the cytotoxic effects of D.

Results: GH protects MDA-MB-231 cells from the cytotoxic effects of D but does not influence MCF-12A cell viability. The GH receptor antagonist Pegvisomant (Peg) reduces GH-induced DNA synthesis also in MDA-MB-231 cells. In addition, in both MDA-MB-231 and MCF7 cells GH does not revert D-induced G2/M accumulation, but significantly reduces basal and D-induced apoptosis, an effect blocked by Peg. GST activity is not implicated in the protective effects of GH, while D-induced apoptosis depends on JNK activation and GH reduces both basal and D-stimulated JNK transcriptional activity and phosphorylation.

Conclusions: In human BC cell lines GH directly promotes resistance to apoptosis induced by chemotherapic drugs independently of ER expression by modulating JNK, further supporting the hypothesis that GH excess might hamper cytotoxic BC treatment and that GH receptor antagonism may represent a new therapeutic pathway also in ER negative BC.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.