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Open Access Highly Accessed Research article

Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines

Ji Eun Kim16*, Clare Stones12, Wayne R Joseph1, Euphemia Leung1, Graeme J Finlay12, Andrew N Shelling3, Wayne A Phillips5, Peter R Shepherd24 and Bruce C Baguley14

Author affiliations

1 Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand

2 Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand

3 Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand

4 Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand

5 Department of Surgery, Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre and University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia

6 Auckland Cancer Society Research Centre, Private Bag 92019, The University of Auckland, Auckland, New Zealand

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Citation and License

BMC Cancer 2012, 12:141  doi:10.1186/1471-2407-12-141

Published: 4 April 2012

Abstract

Background

The phosphatidylinositol-3-kinase (PI3K-PKB), mitogen activated protein kinase (MEK-ERK) and the mammalian target of rapamycin (mTOR- p70S6K), are thought to regulate many aspects of tumour cell proliferation and survival. We have examined the utilisation of these three signalling pathways in a number of cell lines derived from patients with metastatic malignant melanoma of known PIK3CA, PTEN, NRAS and BRAF mutational status.

Methods

Western blotting was used to compare the phosphorylation status of components of the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways, as indices of pathway utilisation.

Results

Normal melanocytes could not be distinguished from melanoma cells on the basis of pathway utilisation when grown in the presence of serum, but could be distinguished upon serum starvation, where signalling protein phosphorylation was generally abrogated. Surprisingly, the differential utilisation of individual pathways was not consistently associated with the presence of an oncogenic or tumour suppressor mutation of genes in these pathways.

Conclusion

Utilisation of the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways in melanoma, as determined by phosphorylation of signalling components, varies widely across a series of cell lines, and does not directly reflect mutation of genes coding these components. The main difference between cultured normal melanocytes and melanoma cells is not the pathway utilisation itself, but rather in the serum dependence of pathway utilisation.

Keywords:
Phosphatidylinositol-3-kinase; ERK; mTOR; Phosphorylation; Melanoma and Melanocyte