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Poster Display session 1

5208 - Characterisation of growth hormone signal transduction in primary melanoma cell lines

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Basic Science

Tumour Site

Presenters

Karla Sousa

Citation

Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238

Authors

K.S. Sousa1, K. Tran1, S. Kolekar1, L. Jain2, Y. Wang2, P.R. Shepherd1, J. Perry2

Author affiliations

  • 1 Molecular Medicine And Pathology, The University of Auckland, 1123 - Auckland/NZ
  • 2 Liggins Institute, The University of Auckland, 1123 - Auckland/NZ

Resources

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Abstract 5208

Background

Growth hormone (GH) signalling is initiated by binding of GH to the GH receptor (GHR) and activation of Janus kinase 2, which in turn, promotes phosphorylation of STAT5, PI3K/AKT and MAPK. High levels of GHR expression have been reported in melanoma. This project aims to characterise GH signalling in primary melanoma cell lines and identify cell lines which respond to GH and GHR inhibition, with a view to testing in preclinical xenograft studies.

Methods

Over 24 cell lines established at the Auckland Cancer Society Research Centre (ACSRC) in New Zealand were tested for response to GH, prolactin (PRL) and a GHR antagonist, by assessing STAT5 phosphorylation by western blot. mRNA expression was assessed by Nanostring PlexSet. Endogenous protein was assessed by ELISA.

Results

From the panel of melanoma cell lines, 62% responded to GH stimulation and GHR inhibition. mRNA expression analysis demonstrated that the IGF1 receptor and GHR were highly expressed across cell lines. Most of the cell lines expressing GHR mRNA responded to GH. GH1 mRNA was expressed at very low levels in a subset of cell lines, and ELISA analysis confirmed the presence of endogenous GH protein. siRNA-mediated knockdown of the GHR reduced GHR mRNA expression and STAT5 phosphorylation by GH. GH increased cell viability in a subset of melanoma cell lines. A vemurafenib-resistant melanoma cell line and B16/F10 mouse cell line were also sensitive to GH and GHR inhibition. Exon analysis will be performed for GH and related genes.

Conclusions

In this study, we have demonstrated GH stimulates signal transduction and promotes enhance of viability of primary melanoma cell lines, and that GHR blockade prevents this effect, indicating that blocking GHR signalling might be a useful strategy to treat melanoma. The next step is to understand whether GHR inhibition plays a role in regulating tumour growth in vivo.

Clinical trial identification

Editorial acknowledgement

Li Family PhD Scholarship.

Legal entity responsible for the study

Peter Shepherd.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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