Page 149 - Concise Pathology for Exam Preparation ( PDFDrive )

134 SECTION I General Pathology

Q. Differentiate between anti-oncogenes and proto-oncogenes.

Ans. Differences between anti-oncogenes and proto-oncogenes are enlisted in Table 6.6.

TABLE 6.6. Differences between anti-oncogenes and proto-oncogenes
Features Anti-oncogenes Proto-oncogenes
Other name Tumour suppressor genes Precursor genes for oncogene
Function They suppress cell proliferation, and promote differ- They promote normal cell growth and dif-
entiation and maturation of cells ferentiation
Inheritance Recessive. Homozygous inactivation, ie, loss of both Dominant. Mutation in a single copy may
normal copies of gene is required for carcinogenesis lead to oncogenic conversion
Action Act passively, ie, cancer-promoting genes dominate Act actively, ie, gene products of oncogenes
and lead to tumour formation due to loss of normal directly lead to tumour formation
function of anti-oncogenes
Examples P53, RB gene, BRCA-1 and 2, TGF-b, APC, WT-1 and NF myc, N-myc, erbB1/2/3

Q. Enumerate the steps involved in carcinogenesis.
Ans. Carcinogenesis is a multistep process (Flowchart 6.2).

Acquired or Normal cell
environmental DNA repair
DNA-damaging agents
DNA damage
INITIATION OF CELL Activation of growth- Failure of DNA repair Inherited mutations

Mutations in the genome of somatic cells
Abnormalities in genes
Inactivation of tumour
suppressor genes
promoting genes
regulating apoptosis
Decreased apoptosis
PROGRESSION Malignant neoplasm
Clonal expansion

Angiogenesis New mutations
Invasion/metastasis
FLOWCHART 6.2. Steps involved in carcinogenesis.

Q. Write briefly on role of cyclins, CDK (cyclin-dependent kinases)
and CDK inhibitors in regulating G 1 /S cell cycle transition.
Ans. Cyclin D, the first cyclin to increase in the cell cycle, appears in mid-G phase, but is
no longer detectable in the S phase. There are three forms of cyclin D, named Dl, D2 and
D3; but to simplify matters, the general term ‘cyclin D’ is used. Cyclin D, like other cyclins,
is unstable and is degraded through ubiquitin—proteasome pathway. During the
G phase of the cell cycle, cyclin D binds to and activates CDK4, forming a cyclin D–CDK4
complex. This complex plays a critical role in the cell cycle by phosphorylating the retino-
blastoma susceptibility protein (pRB). ‘The phosphorylation of RB is a molecular
ON–OFF switch for the cell cycle.’ In its hypophosphorylated state, RB prevents cells
from replicating by forming a tight, inactive complex with the transcription factor E2F.
Phosphorylation of RB dissociates the complex and releases the inhibition on E2F
transcriptional activity (see Flowchart 6.3).

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