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Blok Oncology: Biochemistry Department Medical Faculty USU
Blok Oncology: Biochemistry Department Medical Faculty USU
TUMOR GENETICS
PROTOONCOGENES
ONCOGENES TUMORSUPPRESSOR
GENES
TUMOR MECHANISM
HOW
TO DETECT A TUMOR HOW TO DIAGNOSED HOW TO UNDERSTAND THE MECHANISM HOW ARE THE MOLECULAR PATHWAY IN WHAT CONDITION COULD WE TREAT THE TUMOR WHAT KIND OF TREATMENT
Genes that possess the ability to cause cellular transformation. Act in a dominant fashion, either overexpression or activating mutations.
Cellular transformation. morphologic changes, loss of contact inhibition, anchorage independent growth, ability to form tumors when transplanted into nude mice.
Proto-oncogene.
Potential to become activated into a cancer causing oncogene. Have been found in all multicellular organisms. Would be involved : basic essential functions of the cell related to control of cell proliferation and differentiation. In normal cell : expression is tightly controlled.
Protooncogen products
SIS
ABL
SRC RAS
FMS
MOS
ERB-B1
Cell Cycle
Cell-cycle
control system is based on cyclically activated protein kinases : -Cdks (cyclin dependent kinases) -Cyclins (cdk regulator protein), without cyclins cdk is inactive.
Proto-oncogenes
1.Growth
Factors
Stimulate cells in stationary stage to enter the cell cycle. Occurs in a two stage process :
Stimulation
to proceed into G1 provided by PDGF,EGF,followed by progression factors :IGF to progress through the cell cycle.
2.Growth
factor receptors
Link the information from extracellular environment (GF) to a number of different intracellular signaling pathways. The most important : transmembrane receptor tyrosine kinases.
3.
Signal transducers.
Cytoplasmic nonreceptor tyrosine kinases. Proteins with enzyme activity such as phospholipase C, PI3-K Adaptor proteins : Grb2 SH2 and SH3 domain. Three major pathways : PI3-kinase (PI3-K/AKT pathway, RAS/mitogenactivated protein kinase (MAPK) pathway, JAK/STAT pathway.
4.
G-Protein
ANY QUESTIONS??
CARCINOGENESIS
MOLECULAR
Structural alteration.
an important role in tumorigenesis. Involved in the control of abnormal cell proliferation. Loss or inactivation : association with the development of malignancy.
Viral Oncogene
Three
1.
Persistent infection chronic inflammation repeated cycles of cell damage and cellular proliferation accumulate genetic mutations initiation and promotion of cancer .
2.Direct
participation of infectious agents in the transformation of the cell through activation of cellular oncogene pathway.
3.
Relevant to HIV : infection may result in immunosuppression and decreased recognition of infected or transformed cell by host immune system.
Gene
TRANSCRIPTION
Degradation
MODIFICATION / PROCESSING
mRNA
Degradation Transport
mRNA CYTOPLASM
Active degradation
inactive
TRANSLATION
Protein
Degradation
Insertional mutagenesis
Oncogene transduction Affect expression or function of cellular growth and differentiation genes.
( the only human retrovirus known to directly cause cancer).
NO
RNS ONOO-
N2O3
Protein Damage
(DNA Repair Enzymes, Caspases)
4HNE
(4-hydroxynonenal)
Apoptosis
Programmed
cell death Intracellular machinery responsible for apoptosis is called caspases. Caspases
Synthesized
in the cell as inactive precursor called procaspases Usually activated by cleavage at aspartic acids by other caspases.