Page 150 - Concise Pathology for Exam Preparation ( PDFDrive )

6 Neoplasia 135

External signals (growth factors, integrins)

Activation of MYC, RAS and other genes

Synthesis of cyclin D

Cyclin D + CDK4 form an active complex
P16, INK4, P21
RB phosphorylation in E2F/DP1/RB complex
(in its hypophosphorylated form, RB binds to and sequesters a transcription activator called E2F; RB is
removed from E2F by phosphorylation and free E2F is made available)

Free E2F

Cyclin E transcription

Cyclin E

Cyclin E/CDK 2 (active complex)
P27
G1 S
Note: The cell cycle is blocked by P21, P27, P16 and INK4.
FLOWCHART 6.3. Role of cyclins, CDKs and CDK inhibitors in regulating G1/S cell cycle
transition.

Q. Write in detail on cancer-related genes and their effect on cell
growth.
Ans. Alterations in the controlling genes, typically by mutation, are major genetic hall-
marks of cancer and include:
Excessive and Autonomous Growth

• Genes that promote autonomous cell growth in cancer cells are called oncogenes and
their normal cellular counterparts are called proto-oncogenes.
• Proto-oncogenes are physiological regulators of cell proliferation and differentiation,
and are often involved in signal transduction and execution of mitogenic signals, usually
through their protein products.
• Oncogenes are mutated forms of normal proto-oncogenes, different from the latter in
the following ways:
(a) Presence of mutation/s in the structure of the gene
(b) Ability to promote autonomous and excessive cellular proliferation in the event of
overexpression, even in the absence of normal mitogenic signals
• Activation of oncogenes can be induced by
(a) Point mutation and deletion (as in RAS oncogene implicated in carcinoma of colon
and pancreas)
(b) Chromosomal translocation, as in Philadelphia chromosome (translocation of C-ABL
proto-oncogene from chromosome 9 to chromosome 22) and translocation of
c-MYC proto-oncogene from chromosome 8 to chromosome 14 (seen in 75% cases
of Burkitt lymphoma)
(c) Gene amplification (chromosomal alterations that result in increased number of copies
of a gene) as in the case of n-MYC implicated in neuroblastoma, and ERB-B2 in breast
and ovarian cancer. The expression of oncogenes can be regulated by microRNAs

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