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.
Resources from the same session
5729 - Expression of mutant p53 affects cancer cell sensitivity to topotecan
Presenter: Rimma Mingaleeva
Session: Poster Display session 1
Resources:
Abstract
5725 - Breast cancer organoids a new tool for the prediction of drugs penetration and patient’outcome
Presenter: Giuseppina Roscigno
Session: Poster Display session 1
Resources:
Abstract
5680 - Aptamer-mediated exosomes detection for early breast cancer identification.
Presenter: Cristina Quintavalle
Session: Poster Display session 1
Resources:
Abstract
2460 - MicroRNA-181c promotes tamoxifen resistance in breast cancer cells via upregulation Akt/mTOR axis
Presenter: Alexander Scherbakov
Session: Poster Display session 1
Resources:
Abstract
3751 - Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Presenter: Sandhya Sreedharan
Session: Poster Display session 1
Resources:
Abstract
4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.
Presenter: Joao Pinto
Session: Poster Display session 1
Resources:
Abstract
4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program
Presenter: Ana Monteiro
Session: Poster Display session 1
Resources:
Abstract
5340 - Quantitative imaging and characterization of collagen patterns in high grade serous ovarian carcinoma (HGSOC)
Presenter: Ruby Huang
Session: Poster Display session 1
Resources:
Abstract
4209 - Semiquantitative assessment of vimentin expression in prostate cancer (PC)
Presenter: Marina Puchinskaya
Session: Poster Display session 1
Resources:
Abstract
3309 - Heat Shock Protein 90 chaperones and Protein Kinase D3 regulates androgen-independent prostate cancer development
Presenter: Attila Varga
Session: Poster Display session 1
Resources:
Abstract