Question

You have previously used radiation therapy to induce cell apoptosis in a mouse tumor model in which FGF is over-expressed. Recently, you notice that this therapy is no longer effective and the tumor continued to grow rapidly. Genomic sequencing revealed that those tumor cells have acquired a new loss-of-function mutation in the tumor-suppressor gene Pten, whose protein product normally acts as a phosphatase to dephosphorylate PIP3 into PIP2. Based on this information, you have an idea of why the tumor cells are now radiation- resistant. Please explain how the tumor cells underwent apoptosis early on and how they were protected from apoptosis after acquiring the Pten mutation. You may want to DRAW the pathway and explain your reasoning.

Class: Cell Biology

Answer 1

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay.

PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly.[8] It is a target of many anticancer drugs.

The PTEN protein is widely expressed throughout the body. PTEN protein acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3). PTEN specifically catalyses the dephosphorylation of the 3` phosphate of the inositol ring in PIP3, resulting in the biphosphate product PIP2 (PtdIns(4,5)P2). This dephosphorylation is important because it results in inhibition of the Akt signaling pathway, which plays an important role in regulating cellular behaviors such as cell growth, survival, and migration.

PTEN also has weak protein phosphatase activity, but this activity is also crucial for its role as a tumor suppressor. PTEN's protein phosphatase activity may be involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly.

Many cancerous tumors possess a genetic mutation that disables a tumor suppressor PTEN.inactivation of PTEN allows tumors to resist radiation therapy. The gene produces a protein that acts as a tumor suppressor by preventing cells from growing and dividing too rapidly. Tumors with PTEN mutations are often resistant to radiation therapy. It is because PTEN-deficient cells have defective checkpoints. Checkpoints assess whether a cell is healthy enough to continue growing and dividing. The results indicate that to increase radiation sensitivity in tumors with PTEN mutations, it will be necessary to develop drugs that correct for the faulty checkpoint processes.