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10. Angive visse transkriptions faktorers rolle i carcinogenese: proto-oncogener
og tumor-supressor gener
Devlin, s.217, cc. 5.3
Blicher Pedersen,
Kræftens biolog; s.170
Oncogenes – genes whose mutated or over-expressed products contribute to carcinogenesis.
Proto-oncogenes – normal, non-mutated cellular analogs of the oncogenes.
Their protein products are transcription factors that regulate cell growth and differentiation of a normal cell.
Some proto-oncogene products cell membrane receptors that are involved in transduction of hormonal signals or recognition of cellular growth factors
Tummor-supressor gene - codes for proteins, that can stop the cell's growth and division. If a tumor-supressor gene mutates, it is uable to code for a protein at all or codes for a non-fucntional protein.
A tumor-supressor gene is completely
inactive when both copies of the gene are mutated at the same time.
Thou, a
single copy of the mutant gene causes Li-Fraumeni syndrome, an inherited
condition predisposing to carcinomas of the breast and adrenal cortex, sarcomas,
leukaemia and brain tumors.
p53 - a tumor – suppressor protein, product of a dominant proto-oncogene. It has 3 essential functions:
1. p53 is a transcription factor that, on sensing damaged DNA, promotes transcription of genes that inhibit the cell division, giving the cell time to repair the damage.
2. It can alternatively promote transcription of DNA-repair genes.
3. Under specific circumstances, it can promote programmed cell death – apoptosis.
Thus, the biochemical actions of p53 serve to keep cell growth regulated, maintain the information content of the genome and finally, eliminate damaged cells. All of these functions would counteract neoplastic transformation of a cell.
If the the tumor-supressor gene that codes for p53 mutates, the DNA-binding power of p53 is affected. That way, it can not control the transcription of the genes needed to inhibit cell division, repair DNA or cause apoptosis.
Somatic mutation of p53 is found in about half of all human cancers.
Growth-stimulation of a cell is under control of proto-oncogenes, while growth-inhibition is controled by tumor-suppresor genes.
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