[HTML][HTML] Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines
JE Kim, C Stones, WR Joseph, E Leung, GJ Finlay… - BMC cancer, 2012 - Springer
BMC cancer, 2012•Springer
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 …
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 …
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.
Springer
