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Wednesday, January 09, 2008

Normal cellular counterparts of oncogenes

036. The normal cellular counterparts of oncogenes are important for the following functions except:

1. Promotion of cell cycle progression

2. Inhibition of apoptosis

3. Promotion of DNA repair

4. Promotion of nuclear transcription


3. Promotion of DNA repair


Robbins 7th Edition Page 293, 295





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An oncogene is a modified gene that increases the malignancy of a tumor cell. Some oncogenes, usually involved in early stages of cancer development, increase the chance that a normal cell develops into a tumor cell, possibly resulting in cancer. New research indicates that small RNAs 21-25 nucleotides in length called miRNAs can control expression of these genes by upregulating them.

The first oncogene was discovered in 1982 by Robert Weinberg, a founding member of Whitehead Institute for Biomedical Research and professor of biology at Massachusetts Institute of Technology.


Genes involved in DNA repair are usually not associated with malignant transformation


A proto-oncogene is a normal gene that can become a oncogene, either after mutation or increased expression. They code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through its protein product. Upon activation, it (or its product) becomes a tumor inducing agent, an oncogene. The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are two basic activation types:

Ä A mutation within a protooncogene can cause a change in the protein structure, caused by

o an increase in protein (enzyme) activity

o a loss of regulation

o the creation of a hybrid protein, through a chromosomal aberration during cell division. A distinct aberration in a dividing stem cell in the bone marrow leads to adult leukemia

Ä An increase in protein concentration, caused by

o an increase of protein expression (through misregulation)

o an increase of protein stability, prolonging its existence and thus its activity in the cell

o a gene duplication, resulting in an increased amount of protein in the cell


There are six known classes of protein kinases and related proteins that can become an oncogene:

1. Receptor tyrosine kinases that become constitutively (permanently) active like the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR).

2. Cytoplasmic tyrosine kinases like the Src-family, Syk-ZAP-70 family and BTK family of tyrosine kinases.

3. Regulatory GTPases, for example, the Ras protein.

4. Cytoplasmic Serine/Threonine kinases and their regulatory subunits, for example, the Raf kinase, and cyclin-dependent kinases (through overexpression).

5. Adaptor proteins in signal transduction.

6. Transcription factors.

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