Lecture 21 - Oncogenes and Tumor Suppressor Genes

Cellular oncogenes

These play a role in cellular division, but when mutated, contribute to uncontrolled cell division / cancer

Viral oncogene

A gene from a virus that can induce cancer in host cells. It gives the virus a selective advantage

How do normal cellular oncogenes become cancer causing?

With gain of functino mutations that overstimulate product (cellular replication)

Describe the transfection test

1. DNA of tumor cells are isolated and labeled

2. Bladder cells transfected with different fragments of DNA

3. Cancer cells are identified

4. DNA fragment that induced cancer identified

What is a Ras protein?

A type of small GTP binding and hydrolyzing protein that plays a role in regulating signal transduction pathways involved in cell growth, division, and differentiation. Mutations in these are found in cancer

What does a normal ras protein do?

Hydrolyzes GTP to make itself inactive BECAUSE it only persists when constantly activated by extracellular signals

Describe oncogenic Ras protein signaling

1. Oncogenic c-Ras fails to hydrolyze GTP → permanent activation makes it divide rapidly

2. Gain of function mutation is dominant (wild type allele is recessive and CANNOT stop permant activation

Describe chronic myelogenous leukemia

1. After translocation, c-abll is constitutively produced in white blood cells

2. Kinase activates cell division

3. Dominant activator allele has a gain of function mutation

Burkitt’s lymphoma

c-myc translocated into a region where antibody genes are transcribed at a high rate

What are two broad classes of genes that can contribute to cancer when mutated?

1. Proto-oncogenes

2. Tumor suppressor genes (TSG)

Proto-oncogenes

Actively promotes cell division. When overactivated it results in rapid division. Mutations resulting in cancer are usually dominant

Tumor Suppressor Genes

Represses cell division. Defective form inactive results in a failure to repress division. Mutations resulting in cancer is usually recessive. Usually rare

Describe inherited retinoblastoma

1. An individual inherits one inactivating mutation in one of its RB genes

2. The other RB gene is inactivated by a somatic mutation during eye development

Describe sporadic retinoblastoma

1. An indiviual inherits two active RB genes

2. Both of the RB genes are inactivated by somatic mutations during eye development

what is pRBA?

The retinoblastoma protein that is a tumor suppressor protein that is dysfunctional in many types of cancer

How does pRB function in early G1 phase?

1. pRB binds the #2F family of transcription factors

2. The bound E2F proteins are unable to stimulate transcription of their target genes

Cyclins

Proteins that control the progression of a cell throughout the cell cycle

How do cyclins determine if a cell moves through different stages of the cell cycle?

The concentration of cyclins

p53

A transcription factor that arrests the cell cycle and tells cells to not start replication → This allows for DNA repair

Apoptosis

Programmed cell death that is induced by p53 if DNA repair fails. It limits opportunities for cells to become cancerous

Are cancer causing mutations in p53 dominant or recessive?

They cna be either dominant or recessive alleles