When normal cells are beyond repair they
are eliminated by a process called
‘Apoptosis’.
·
Apoptosis is regulated by two major
genes p53 & Bcl-2
·
Mutations or overexpression of these genes will result in Cancer.
p53 :
P53 or TP53
is a tumour
supressor protein which
is encoded by p53 gene.
In normal cells p53
protein level is low. DNA damage and other
stress signals triggers
the level of
p53 protien resulting in three
major functions.
(a)Growth arrest
(b)DNA repair
(c)Apoptosis
Mutations in wild
type p53
cause abnormal cells to proliferate
resulting in cancer.
P53 mutations with
in area of p53
accumulation are indentified with ‘Immuno-Histo Chemistry(IHC).
B-cell
lymphoma-2(Bcl-2) :
— Bcl-2 is
Apoptosis inhibitor
— Its overexpression is associated
with Hormone Refractory
Prostrate cancer (HRPC).
— More
the expression greater will be the the stage
of disease.
— BCL-2
family has 2 types of apoptosis regulatory molecules
1.death antagonists( examples
:Bcl-2,Bcl-xL,Mcl-1)
2.death agonists(examples
:Bak,Bax,Bcl-xS,Bad,Bid)
— It is considered that defective apoptosis is a feature of
malignant development
— Induction of apoptosis in malignancies is to be aimed
— Detection of apoptosis-related proteins may be of
importance in the prediction of patient’s response to chemo- or radio-therapy
as well as of survival rates
— Chemosensitivity testing, thereby individualised
chemotherapy on the basis of patient-specificity, seems to be promising in the
succesful treatment of malignancies. This testing, thereby, may revolutionize
the way we use anti-cancer drugs in
near future
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