Cell Cycle and Cancer: Focus on Cyclin D1 and CDKs

These flashcards cover key concepts from the lecture on cell cycle dysregulation in cancer, emphasizing the roles of cyclins and CDK4/6.

What is the primary role of Cyclin Dependent Kinases (CDKs) in the cell cycle?

CDKs promote progression through each stage of the cell cycle.

Which CDKs are often associated with the cyclin D family?

CDK4 and CDK6 are commonly associated with the cyclin D family, particularly cyclin D1.

What happens to cyclin levels during the cell cycle?

Cyclin levels fluctuate with the cell cycle.

How does CDK activity vary during the cell cycle?

CDK levels are generally constant, but their activity varies depending on the presence of specific cyclins.

What is the function of the tumor suppressor protein pRB in the cell cycle?

pRB inhibits E2F function, which is crucial for the transition from G1 to S phase.

What does CCND1 gene encode?

CCND1 encodes cyclin D1, a cell cycle regulator and proto-oncogene.

Which cancer types show overexpression of cyclin D1 due to gene amplification?

Mantle cell lymphoma and endometrial carcinomas commonly show cyclin D1 overexpression due to gene amplification.

What laboratory method is used to detect CCND1 gene amplification?

Southern blotting is used to examine CCND1 gene amplification.

How can cyclin D1 levels impact cancer prognosis?

High levels of cyclin D1 can correlate with poor prognosis in cancers such as colorectal carcinoma.

What is one mechanism that leads to cyclin D1 overexpression in cancer?

Increased mRNA stability, leading to higher levels of cyclin D1 protein, is one mechanism for its overexpression.

What is the significance of the G870A polymorphism in the CCND1 gene?

The G870A polymorphism leads to alternative splicing, resulting in cyclin D1b which cannot be regulated by GSK3β.

What are some roles of cyclin D1 independent of CDK4/6 activation?

Binding and sequestering negative regulators of cell cycle progression and controlling gene expression by interacting with transcription regulators.

Which CDK inhibitors are currently approved for cancer treatment?

Only CDK4/6 inhibitors are currently approved for cancer treatment targeting breast and lung cancers.

What effect does the phosphorylation of cyclin D1 by GSK3β have?

Phosphorylation by GSK3β is necessary for the nuclear export of cyclin D1.

What type of cancer is associated with chromosomal translocation resulting in cyclin D1 overexpression?

Mantle cell lymphoma is associated with chromosomal translocations leading to cyclin D1 overexpression.

How does the stability of mRNA affect cyclin D1 protein levels in cancer cells?

Increased mRNA stability prevents quick degradation, resulting in longer persistence of cyclin D1 protein levels in cancer cells.

What is a key regulatory function of E2F transcription factors in the cell cycle?

E2F transcription factors promote entry into the S phase through the expression of genes necessary for DNA replication.

What are the potential consequences of aberrant cyclin D1 activity in cells?

Aberrant activity can lead to increased cell proliferation and contribute to cancer development.