Question

About 30% of all human tumors involve cells expressing mutated Ras oncogenes. Additionally, about 20% of the human tumors involve cells with defective PTEN, a phosphatase that convert PIP3 into PIP2. Based on your knowledge of signal transduction pathways, explain the relationship of these mutated genes with tumor cell proliferation.   

Answer 1

Ras protein is part of Tyrosine kinase pathaway.once the signal molecule binds to tyrosine kinase receptor it get activated and phosphorylate SoS which activates GEF protein that ultimately phosphorylate Ras to convert from inctive form to active form and phosphorylate form of Ras cause activation of several transcription factor which start several proteins that leads to start of cell cycle.

Now if there is mutation in ras gene then protein will remain always in phosphorylated form and always be in switch on mode and leads to proteins synthesis that cause continous cell cycle and leads to cancer.

Similarly IP3 is potent signal molecule which synthesized by GPCR pathway and IP3 binds to Endoplasmic reticulum and cause release of Ca2+ into cytoplasm that leads to activation of calcium dependant pathway and that leads to activation of several cell cycle protein.

Now, phosphatase enzyme cause removal of IP3 to IP2 which leads to switch off the IP3 cascade pathway. If there is mutation of phosphatase enzyme,then IP3 will not converted to IP2 and it remain in active form and hence cascade pathway remain operational and ultimately leads to cancer.

Hope it's clear..thanks