Question 1

What are mitogens and why do cells need them to divide?

Accepted Answer

Mitogens are small proteins or peptides that trigger cell division in multicellular organisms. Unlike bacteria that divide when nutrients are available, most cells in multicellular organisms remain in G0, a non-dividing phase, until mitogens bind to their receptors. Mitogens are secreted in response to stimuli like tissue injury or infection, signaling cells when division is appropriate.

Question 2

How does PDGF trigger the cell cycle after tissue injury?

Accepted Answer

Platelet-derived growth factor (PDGF) binds to tyrosine kinase receptors on cell surfaces, causing receptor dimerization and autophosphorylation. This activates downstream signaling molecules and initiates the MAP kinase cascade, which ultimately activates transcription factors like Myc that increase G1 cyclin expression and drive cell cycle progression.

Question 3

What role does the MAP kinase cascade play in mitogen signaling?

Accepted Answer

The MAP kinase cascade is a signaling pathway activated when mitogens bind to receptors. It begins with Ras activation, followed by sequential phosphorylation of MAP3 kinase, MAP2 kinase, and finally MAP kinase. Active MAP kinase enters the nucleus and activates transcription factors that promote expression of cell cycle genes necessary for division.

Question 4

How do G1 cyclins and Cdks control progression through the cell cycle?

Accepted Answer

G1 cyclins partner with cyclin-dependent kinases (Cdks) to form complexes that phosphorylate the Rb tumor suppressor protein. This phosphorylation releases E2F, a gene regulatory factor that binds DNA and triggers transcription of cell cycle genes. The positive regulators cell cycle cyclins and Cdks are essential for advancing cells from G1 into S phase.

Question 5

How does Rb protein prevent excessive cell growth?

Accepted Answer

Rb protein acts as a tumor suppressor by binding and inhibiting E2F, a transcription factor required for cell cycle gene expression. When mitogenic signals decline, such as during tissue healing, Rb interacts with E2F and blocks its activity. This prevents transcription of genes needed for cell division, stopping excessive growth.

Question 6

Why is EGFR overexpression associated with cancer development?

Accepted Answer

In normal cells, EGFR expression is tightly regulated to match tissue division needs. However, in cancer cells, EGFR is overexpressed or perpetually activated by EGF or mutations, leading to continuous growth signals. This uncontrolled signaling causes abnormal proliferation, tumor invasion, and metastasis, making EGFR a target for cancer therapies.

Question 7

How do monoclonal antibodies target mitogen receptors in cancer treatment?

Accepted Answer

Monoclonal antibodies like trastuzumab and IMC-C225 block activation of overactive EGFR and ErbB2 receptors on cancer cells. By preventing mitogen binding or receptor signaling, these antibodies interrupt growth signals and can induce cell cycle arrest, dedifferentiation, or programmed cell death in tumor cells.

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