2. CONTENTS
1.1. DiscoveryDiscovery
2.2. IntroductionIntroduction
3.3. CancerCancer
4.4. Properties of cancer cellsProperties of cancer cells
5.5. Classes of genes involved in developmentClasses of genes involved in development
a.a. Proto-oncogenesProto-oncogenes
b.b. Tumor suppressor genesTumor suppressor genes
c.c. Genes involved in ApoptosisGenes involved in Apoptosis
6. Carcinogen6. Carcinogen
7. Oncogenic retrovirus7. Oncogenic retrovirus
8. Summery8. Summery
9. References9. References
3. DISCOVERY
• Oncogene: “onco” (cancer) geneOncogene: “onco” (cancer) gene
• 1989 Nobel Prize in Medicine or Physiology:1989 Nobel Prize in Medicine or Physiology:
The Discovery of Cellular Origin of RetroviralThe Discovery of Cellular Origin of Retroviral
OncogenesOncogenes
•J. Michael Bishop(UCSF)J. Michael Bishop(UCSF)
•Harold Varmus (UCSF)Harold Varmus (UCSF)
4. A gene which in certain circumstances can
transform a cell into a tumor cell.
or
Oncogene is the type of gene that is mutated
or changed form of a gene involved in normal
cell growth.
•Oncogenes are also those genes which were
earlier was proto-oncogenes.
INTRODUCTION
5. CANCER
A normal cell undergoes regulated division
differentiation and apoptosis. When normal cells have
lost the usual control theirdivision, differentiation and
apoptosis they become tumorcells.
Tumormay be of two types:
1.Benign tumor - Neoplastic cells remain clustered
togetherin a single mass and can’t spread to othersites.
2.Malignant tumor– Neoplastic cell that do not remain
localized and encapsulated, become invasive and
malignant.
6. COMPARISON OF BENIGN AND
MALIGNANT TUMOR
Characteristics Benign Malignant
Differentiation Well Differentiation Lack
Differentiation
Rate of growth Slow Rapid
Invasiveness Absent Present
Metastasis Absent Present
7. TRANSFORMATION
•The transition of a normal cell to tumorcell is referred to as
Transformation.
•It is a multistep process involving genetic and epigenetic changes and
selection of cells with the increasing capacity forproliferation , invasion
and metastasis.
Process:
Initiation Promotion
ProgressionMetastasis
8. PROPERTIES OF CANCER CELLS
1. Density dependent inhibition
2. Contact inhibition
3. Immortalization
4. Invasiveness & Metastasis
5. Loss of anchorage dependence
6. Lowergrowth factors requirements
7. Failed to undergo apoptosis
9. CLASSES OF GENES INVOLVED IN
DEVELOPMENT OF TUMOR
There are principally three classes of genes
which results in the development of tumor.
I.Proto-oncogenes
II.Tumorsuppressor genes
III.Genes involved in apoptosis
10. PROTO-ONCOGENES
•Normal cellulargenes usually involved in cell growth
orcell division.
•The proteins enclosed forproto-oncogenes include
growth factor, transcription factorand signal
transducers.
•They contribute to the transformation process by
driving cell proliferation to cell death.
Today, morethan40different humanproto-
oncogenes are
known:
•Several types of genetic & epigenetic changes
convert these proto-oncogenes into oncogenes.
11. MECHANISMS OF ACTIVATION
1. Point mutation
A proto-oncogene may converted into an oncogene through a single alteration
of a nucleotide. This alteration may be deletion of base, insertion of extra
base orthe substitution of one base for another.
Eg. RAS proto-oncogenes.
2. Chromosomal translocation
Chromosomal translocation also results in activation of proto-oncogenes. The
conversion of proto-oncogenes into oncogenes is best exemplified by
Burkitt’s lymphoma (type of tumormainly affects the jaw). In Burkitt’s
lymphoma , myc protein is present which goes through the non-
proliferating state. If this myc gene that blocked cell cycle progression
also blocked.
3. Amplification
The most interesting case of amplification involve NMYC in neuroblastoma .
12. TUMOR SUPPRESSOR GENES
•These are those genes that are normally involved
in the inhibition of cell growth and proliferation.
•They directly orin directly inhibit cell growth.
•Directly inhibit cell growth- GATEKEEPERS
•Indirectly inhibit cell growth- CARETAKERS
13. Four broad classes of genes are generally
grouped into tumor suppressor genes
• Genes that regulate or inhibit cell cycle
progression (eg-p16,RB1).
• Genes that promote apoptosis.
• Genes that encode enzymes that participate
in DNA repair.
• Genes that encode checkpoint control
proteins that arrest the cell cycle, if DNA is
damaged (eg-p35).
14. EXAMPLE OF TUMOR SUPPRESSOR GENES
AND THEIR FUNCTIONS
Tumorsuppressor genes Function
BRCA1 and BRCA2 Transcription factor, DNA repair
hMLH1 DNA mismatch repair
NF1 Gtpase
p53 Transcription factor
RB1 Cell cycle checpoint
15. DIFFERENCES BETWEEN ONCOGENES
AND TUMOR SUPPRESSOR GENES
Oncogenes Tumorsuppressorgenes
• Mutation in one of the two
alleles sufficient for
activity :act dominant to
wild-type
• Mutation in both alleles ora
mutation in one followed by a
loss orreduction to
homozygosity in the second
• “Gain of function” of a
protein that signals cell
division
• Loss of function of a protein
• Mutation arises in somatic
tissue, not inherited
• Mutation present in germcell
(can be inherited) orsomatic
cell
• Some tissue preference • Strong tissues preferences
(eg. effect of RB1 gene in
retina)
16. GENES INVOLVED IN
APOPTOSIS
•It is a energy dependent biochemical mechanismof
programmed cell death
Or
Biochemical events lead to characteristics cell
changes and death
•These changes includes blebbing, cell shrinkage,
nuclearfragmentation, chromatin condensation,
chromosomal DNA fragmentation & global mRNA
decay.
•The average adult human loss 50-70 billion cells
each day due to apoptosis.
17. Chemicals
(Benzophrene
& Benzene)
Three classes of carcinogen
agents
Radiations (uv
rad. & gamma
ray)
Biological
(oncovirus)
Carcinogen
Agents that initiate or promote tumor formation are calledAgents that initiate or promote tumor formation are called
Carcinogens.Carcinogens.
Chemical carcinogens have a very broad range of structuresChemical carcinogens have a very broad range of structures
that have little or no obvious structural or biochemical similaritythat have little or no obvious structural or biochemical similarity
to each other.to each other.
18. TWO TYPES OF CHEMICALTWO TYPES OF CHEMICAL
CARCINOGENS:CARCINOGENS:
• Direct- acting carcinogen:Direct- acting carcinogen:
Which act directly without any metabolic activation.Which act directly without any metabolic activation.
• Indirect- acting carcinogen:Indirect- acting carcinogen:
Which require metabolic activation for themWhich require metabolic activation for them
to act as carcinogens.to act as carcinogens.
eg : Aflatoxin ( or mycotoxin)eg : Aflatoxin ( or mycotoxin)
19. ONCOGENIC RETROVIRUSES
1. Cancer is a genetic disease- oncogenesis consists of the
processes that result in growth of cells in which mutations
have accumulated
2. Viruses are a contributing factor in about 20% of all human
cancers
3. Growth properties and morphologies of cultured cells could be
changed upon infection with certain viruses- cells become
transformed
4. Cells become immortal in an early step in oncogenesis-they
continue to grow and divide even though the body has
sufficient numbers of these cells
5. They lose contact inhibition and the need to adhere to a surface
6. They look different, more rounded
20. • Oncogenesis is the result of genetic
changes that alter the expression or
function of proteins that play critical roles
in the control of cell growth and division
• Oncogenic viruses cause cancer by
inducing changes that affect cell growth
and division
• Cancer arises from a combination of
dominant gain of function mutations in
proto- oncogenes and recessive loss of
function mutations in tumor suppressor
genes
ONCOGENIC
VIRUSES
21. Scientists have found many more than 100 new genes
that can cause cancer if they become mutated. The
discovery was part of largest survey of the human
genome to date, which also suggests that the number of
cancer gene is far larger than previously thought. ‘‘Thus
far, there are approximately 350 genes in human
genome that have been shown to be cancer gene,” said
Mike Stratton, co-leader of the Cancer genome Project
at the Wellcome Trust Sanger Institute, Cambridge.
““Study Find Many New CancerStudy Find Many New Cancer
Genes”Genes”
22.
23.
24. REFERENCES
•R.A.Weinberg. The Bilogy Of Cancer, Chapter 4,Garland Press ,
2007
•Cancer Medicine-8th
Ed. Edited By D.W. Kufe et al.
•Section 1-Cancer Biology
•pathfinderpublication.in