Tumourigenesis and cancer signalling Flashcards by Alysha Afsar

what is tumourigenesis?

production or causation of tumours

production of new growth

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what is cancer signalling?

abnormal cellular/molecular mechanisms that lead to cancer

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what is a tumour?

“swelling” – any tissue mass: benign or malignant

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define neoplasia?

New growth: benign or malignant

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define cancer?

Malignant tumour with potential to metastasize

Synonymous with neoplasia

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what is differentiation in terms of tumour?

Morphology of tumour cell compared to normal
Well-differentiated
Poorly differentiated

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define mutation?

Change in one or more DNA bases from normal sequence

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define carcinogenesis?

Processes involved in the onset/development of cancer

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define metaplasia?

Reversible replacement of one cell type with another
Frequently associated with development of malignancy in metaplastic tissue
May induce dysplasia

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what is dysplasia?

Altered cell maturation, orientation & tissue architecture

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what is anaplasia?

Lack of differentiation

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what is the epidemiology of cancer?

Predominately a disease of middle-aged & elderly

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what can the distribution of cancer indicate?

underlying causes

e.g. Hepatocellular carcinoma – SE Asia & Africa, due to high prevalence of hepatitis B & C

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what are major predisposing factors of cancer?

smoking and diet

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what are some environmental factors that contribute to cancer?

Chemical carcinogenesis
Radiation
Viruses & cancer

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what are some genetic factors that contribute to cancer?

Familial cancer syndromes

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what are the effects of ionising radiation?

Direct DNA damage
Indirect DNA damage
Bystander effects
Adaptive response

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what are the effects of UV radiation?

Direct DNA damage

Affects protein and lipid function – changes in cell signalling

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what is the initation step in carcinogenesis?

carcinogen induces non-lethal mutations in cell

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what is the promotion step in carcinogenesis?

Initiated cell proliferates

(clonal expansion); allows additional mutations to accumulate

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what is the progression step in carcinogenesis?

Accumulation of multiple mutations results in invasive phenotype

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what are examples of carcinogenesis initiators?

UV radiation
Cisplatinum
Asbestos
Alkylating drugs

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what are some examples of carcinogenesis promoters?

Hormones
alcohol
chronic irritation or wounding

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what are examples of abnormal proliferation and cellular immortalisation?

Uncontrolled proliferation

Prolonged or indefinite life span

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what is polyploidy?

increased nuclear DNA - nuclear hyperchromasia

what is aneuploidy?

inexact multiples of DNA per cell

what are examples of abnormal nuclear DNA in tumour cells?

- polyploidy - aneuploidy - chromosomal translocations or rearrangements

what happens to mitotic and apoptotic activity in tumour cells?

- Increased mitotic activity in malignant tumours - Increased cellular proliferation - Deregulation of apoptosis

what are the 2 main groups of teens implicated in cancer?

oncogenes | tumour suppressors

how can the implication of oncogenes lead to cancer?

the lack of inhibition or gain of function will lead to cancer

how can the implication of tumour suppressors lead to cancer?

the increased inhibition or loss of function of which will lead to cancer

what are examples of oncogenes?

- cyclins - CDKs - E2F - MYC - Mdm2

what are examples of tumour suppressors?

- RB - p53 - p21, p27, P57 (CIP/KIP/WAF) - p14/ARF -p16/INK4a, p17, p18, p19 TGF-B receptor BRCA1, BRCA2 ATM

what are proto-oncogenes?

Normal part of genome | Promote cell growth

what are oncogenes?

Mutated versions of proto-oncogenes | they lead to Uncontrolled growth

what is the first step in the process of a proto-oncogene becoming an oncogene?

Point mutation of proto-oncogene --> | encodes oncoprotein – differs from normal protein

what is the second step in the process of a proto-oncogene becoming an oncogene?

Gene amplification of DNA segment that includes a proto-oncogene --> Over-expression of encoded protein

what is the last step in the process of a proto-oncogene becoming an oncogene?

Chromosomal translocation so that growth-regulatory gene is under control of different promoter --> Inappropriate expression of encoded protein

what is important about gene amplification and chromosomal translocation in the forming of oncogenes?

these mechanisms generate oncogenes that produce proteins identical to normal protein

what is the function of tumour suppressor genes?

normally act to inhibit cell proliferation

what happens to tumour suppressor genes in tumour cells?

they are lost/inactivated in tumour cells

what are the characteristics of benign tumours?

- Non-invasive, remain localised - Slow growth rate - Close histological resemblance to parent tissue

what are the characteristics of malignant tumours?

- Invasive, capable of metastasis - Rapid growth rate - Variable histological resemblance to parent tissue

how are tumours classified?

- behavioural - benign or malignant | - histogenic - tissue of origin

what are the characteristics of an intraepithelial neoplasia?

Dysplasia Carcinoma in situ Early detection to avoid invasion

what are the steps of the metastatic sequence?

- Detachment - Invasion - Intravasation - Evasion - Adherence - Extravasation

what are the possible mediators of detachment in the metastatic sequence?

loss of surface adhesion molecules e.g. cadherins

what are the consequences of detachment?

migration of individual cells enabled

what are the possible mediators of invasion the metastatic sequence?

- metalloproteinases - up-regulation of integrin expression - down-regulation of tissue inhibitors of metalloproteinases

what are the consequences of invasion in the metastatic sequence?

erosion of tissue boundaries

what are the possible mediators of intravasation in the metastatic process?

- metalloproteinases | - down-regulation of tissue inhibitors of metalloproteinases

what are the consequences of intravasation in the metastatic process?

access to vascular routes of dissemination

what are the possible mediators of evasion in the metastatic process?

- reduced expression of MHC class I antigen | - shedding of ICAM-1 blocks T-cell receptor

what are the consequences of evasion of host defences?

survival against host defences

what are the possible mediators of adherence in the metastatic sequence?

binding of CD44 to endothelial ligand

what are the consequences of adherence in the metastatic sequence?

arrest of movement by adhesion to endothelium

what are possible mediators of extraversion in the metastatic sequence?

- interns | - Laminin receptor

what is the consequence of extravasation in the metastatic process?

colonisation of site of metastasis

what are the traits of tumours?

- Evasion of apoptosis - Self-sufficiency in growth signals - Insensitive to growth inhibition signal - Sustained angiogenesis - Limitless replicative potential - Ability to invade and metastasise

what are the ways to pathologically diagnose tumours?

Biopsies Cytology Tumour staging & grading

what is an excisions biopsy?

entire lesion removed

what is an incisional biopsy?

fairly large, representative sample taken

what is a needle biopsy?

thin core of tissue removed

what is a disadvantage of needle biopsies?

potential for sampling error

what is cytology?

a sample of body fluids relies on the appearance of individual cells

what is grade 1 of tumour grading?

well differentiated

what is grade 2 of tumour grading?

moderately differentiated

what is grade 3 of tumour grading?

poor differentiated

what is stage A in Dukes' staging?

confined to submucosa or muscle layer

what is stage B in Dukes' staging?

invasion through muscle layer

what is stage C in Dukes' staging?

tumour in lymph nodes

what happens in the development of colorectal cancer?

- increasing DNA damage - DNA mutations - APC gene - KRAS oncogene - BRAF gene - MSI

what is the APC gene responsible for in the development of colorectal cancer?

chromosome segregation

what is the KRAS oncogene responsible for in the development of colorectal cancer?

cell growth, differentiation, survival motility

what is the BRAF gene responsible for in the development of colorectal cancer?

cell growth, apoptosis

what is MSI responsible for in the development of colorectal cancer?

uneven replication of DNA