Oncogenes and tumour suppressor genes
Transcript of Oncogenes and tumour suppressor genes
Licentious division - prostate cancer cells during division.
Cancer
not a single disease; heterogeneous group of disorderscharacterized by the presence of cells that do not respond to the normal controls on division.
Rather than lacking function, cancer cells reproduce
at a rate far beyond the normally tightly regulated
boundaries of the cell cycle.
occur due to an alteration of a normal biological
process — cell division.
Induction of malignant transformation with chemical or physical carcinogens appears to involve multiple steps and at least two distinct phases:
initiation and promotion.
The signals that regulate cell division fall into two basic types:
molecules that stimulate cell division and
those that inhibit it.
Genes that have been implicated in carcinogenesis are dividedinto two broad categories:
Tumor-suppressor genes and
Oncogenes.
Tumor-suppressor genes
Encode proteins that
restrain cell growth and
prevent cells from becoming
malignant.
Act recessively since both
copies must be deleted or
mutated before their
protective function is lost.
Oncogenes
> Encode proteins that promote the loss of
growth control and malignancy.
Oncogenes arise from
Proto-oncogenes—genes that
encode proteins having a role in a cell’s
normal activities.
Mutations that alter either the protein or
its expression cause the proto-oncogene to
act abnormally and promote the formation
of a tumor.
MESSAGE The proteins that oncogenes encode areactivated in tumor cells, whereas the proteins that tumor suppressorgenes encode are inactivated.
Five broad classes of proteins are generally recognized as being encoded by tumor-suppressor genes
Intracellular proteinsthat regulate or inhibit progression through a
specific stage of the cell cycle (e.g., p16 and Rb)
Receptors or signal transducers for secreted hormones or developmental signals that inhibit cell proliferation (e.g., TGF)
Checkpoint-control proteins that arrest the cell cycle if DNA is damaged or chromosomes are abnormal (e.g., p53)
• Proteins that promote apoptosis
• Enzymes that participate in DNA repair
TP53 : the guardian of genome…
The product is a protein of 53 kilodaltons(hence the name).
>The p53 protein prevents a cell from completing the cell cycle if its DNA is damaged or the cell has suffered other types of damage.
Loss-of-Function Mutations in Tumor-Suppressor
Genes Are Oncogenic
• deletions or point mutations
• methylation of cytosine residues in the promoter or other control elements.
Loss of Heterozygosity
Subsequent loss or inactivation of the normal allele in a somatic cell, referred to as loss of heterozygosity (LOH),is a prerequisite for cancer to develop.
[Micrographs by E. R. Fearon and K. Cho. From W. K. Cavanee and R. L. White, Scientific American, March 1995, pp. 78–79.]
Gain-of-Function Mutations ConvertProto-oncogenes into Oncogenes
• Point mutation(i.e., change in a single base pair) in a
proto-oncogene that results in a constitutively activeprotein product
• Chromosomal translocation that brings a growth regulatory
gene under the control of a different promoterthat causes inappropriate expression of the gene
Five broad classes of proteins are generally recognized as being encoded by tumor-suppressor genes
• Amplification (i.e., abnormal DNA replication) of a
DNA segment including a proto-oncogene, so thatnumerous copies exist, leading to overproduction of the encoded protein
[Adapted from B. Vogelstein and K. W. Kinzler, 1993, Trends Genet. 9:138.]
Model of sequential genetic alterations leading to metastatic colon cancer.
Although oncogenes or mutated tumor-suppressor
genes or both are required to produce cancer,
mutations in DNA repair genes
can increase the likelihood of acquiring mutations
in these genes.
Cancer is currently treated by surgery, chemotherapy, and radiation.
Several other strategies are being tested; these include # immunotherapy,# inhibition of proteins encoded by oncogenes, # inhibition of angiogenesis.
REFERENCES
1. Molecular Cell Biology- Lodish, Baltimore et al, Freeman
and Co.
2. Cell and Molecular Biology- Concepts and Experiments-
Karp (2012) 5th edn.,
John Wiley and sons
3. www.youtube.com
4.http://www.biooncology.com/