By:Hussain albaharna

Oncogenes and proto-oncogenes

• Scientists discovered in the late 1970s that a specific
gene type plays a major role in the carcinogenesis of the
cell, the so-called proto-oncogenes
• Oncogenes are mutated forms of proto-oncogenes
whose functions are to encourage and promote the,
normal growth and division of cells. When proto-
oncogenes mutate to become carcinogenic oncogenes,
the result is excessive cell multiplication
• Generally, proto-oncogenes code for cellular proteins
that relay signals, to a cell's nucleus, stimulating growth
 Oncogenes and proto-oncogenes
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• Proto-oncogenes activation to oncogenes
may result in:
• overproduction of growth factors.
• flooding of the cell with replication signals .
• uncontrolled stimulation in the.
intermediary pathways and/or
• unrestrained cell growth driven by
elevated levels of transcription factors.
 Mode of oncogene activation
• There are several ways of transforming proto-
oncogenes into oncogenes:
• Point mutation (alterations in the genetic code)
• Deletion (truncated EGE receptor)
• Translocation (chromosomal rearrangements,
Burkitt i lymphoma)
• Gene amplification (double minutes, eg. erb-B in
glioblastoma)
• Viral insertion (retroviral transduction)
 So … proto-oncogene is
Any gene that could code for:
• Growth factor
 So … proto-oncogene is
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Any gene that could code for:

• Growth factor
• Growth factor receptor
 So … proto-oncogene is
(continue)

Any gene that could code for:

• Growth factor
• Growth factor receptor
• Intracellular signaling molecule, or
 So … proto-oncogene is
(continue)

Any gene that could code for:

• Growth factor.
• Growth factor receptor.
• Intracellular signaling molecule, or,
• Molecule that alter the rate of
transcription.
 Apoptosis
• Apoptosis or "programmed cell death" in which
the cell actively participates in its demise in
response to a tumor suppressor gene known as
p53.
• It is characterized by cell shrinkage, chromatin
condensation, cytoplasmic blebbing, and DNA
fragmentation whereas mitochondria and other
cytoplasmic organelles remain intact during the
early stages.
 Are all cancers caused by
? oncogenes
• The roles of Non-genetic mechanisms in cancer
induction:
• Some chemicals, called promoters can potentiate the
activity of electrophilic carcinogens. Phorbol esters
(PEs) cause non-genetic cellular changes that often
mimic transformation by activating protein kinase C.
Long-term treatment with PEs leads to permanent
cellular alterations that may or may not be genetic.
• Epigenetic alteration leading to a teratocarcinoma.
These tumor cells revert to normal when they are
implanted into early embryos but if they are injected into
adult mice, they form lethal tumors. Thus their malignant
state is conditional on their environment.
 Antisense RNA for human therapy
• Messenger RNA (MRNA), is single-stranded. it's
sequence of nucleotides is called "sense"
because it results in a gene product (protein)
• Antisense RNA bind to and deactivates mRNA.
• Putting antisense RNA in the ribosome,
facilitates the meeting of mRNA and antisense
RNA and the inactivation of the Messenger
• Antisense RNA that is complementary to the
proto-onccgene BCL-2 is being examine as a
possible therapy for certain B-cell lymphomas
and Ieukemias.