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17th January |
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Sprouty in Cancer
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IMCB’s latest PhD Graduate - Lo Ting Ling
Abstract
Inappropriate activation of the Ras-mitogen activated protein kinase (MAPK) signalling pathway has long been implicated in many types of human cancers, implying that strict regulation of Ras-MAPK signalling is important for regulating the growth and survival of cells. Sprouty (Spry) proteins are endogeneous inhibitors of Ras/MAP kinase pathway that play an important role in the remodeling of branching tissues such as in development of the lung, kidney tubules and vascular system. This study evaluates the potential role of Sprouty proteins in cancer. T he expression of Sprys in various types of cancer has been analyzed and Spry 1 and 2 were found to be significantly downregulated in more than 90% of breast cancers. Spry 2 was also found to be down-regulated in liver cancers. Analysis of the possible genetic and epigenetic mechanisms causing the down-regulation of Spry genes indicates that methylation is not responsible for down-regulation observed in breast and liver cancers. In liver cancers, no loss of heterozygosity was observed in the microstatellite markers flanking the hSpry2 gene locus. In this study, the suppressed expression and therefore function of Spry was found to potentiate aberrant signaling in tumorigenesis. Knock down of Spry2 expression in NIH3T3 cells was found to cause NIH3T3 cells to be more susceptible to growth factor induced transformation. Sprys were also able to inhibit colony formation induced by Polyoma Middle T antigen (PyMT) oncogene via the inhibition of the activation of the Ras/ERK signaling pathway.
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