Ritu's Biology Hub

What Is Oncogenesis?

Oncogenesis includes processes that result in the growth of successive population of cells in which mutations have accumulated. Cancer may be caused by spontaneous or induced mutations, carcinogens or infectious agents.

Properties Of Transformed Cells

1. In Vitro

• Increase in number and size of nucleus leading to genetic instability
• Polyploidy ie., increase in the number of chromosomes
• Elevated levels of telomerase activity
• Metabolic changes – divide and grow at rapid rates
• Lack of contact inhibition – Normal cells stop replicating when they come in contact with one another whereas cancerous cells continue to divide and pile on top of each other into a foci. Foci originate from a single parent cell
• Anchorage independent growth
• Grow independently without the requirement of growth factors as they synthesize their own cytokines
• Undergo loss of cell cycle control mechanism
• Changes in membrane structure and functions. Abnormal cells display tumour specific carbohydrate antigens on cell surface
• When such cells are injected into healthy mice they trigger tumour formation

2. In Vivo

• Increase in oncogene protein synthesis because the cellular oncogenes (c-onc) have undergone translocation, duplication or mutation
• Loss of tumour suppressor gene function due to deletion or deleterious mutations
• Alteration of DNA methylation patterns
• Increased or unregulated levels of growth factors needed
• Uncontrollable cell division
• Increased levels of enzymes involved in nucleic acid synthesis and lytic enzymes such as protease, collagenase, glycosidase etc.
• Elevated levels of telomerase activity
• Can avoid host immunesurveillance response

Cancer Is A Multistep Process

• Must bypass apoptosis
• Circumvents need for growth signals from other cells
• Escapes immunosurveillance
• Commands its own blood supply
• May metastasize
• Mutations in cellular tumour suppressor genes may be required to attain full malignancy

1. Retroviruses

• May cause cancer in 3 ways
  1. May carry viral oncogenes (v-onc) in host cells
  2. Increase expression of c-onc
  3. Inactivate tumour suppressor gene
• RNA genome – 2 copies of ss-RNA. The RNA is copied into DNA which is then integrated into host chromosome
• 3-4 genes between unique and repetitive sequences
• 7-12 kb length genome
• 3 main genes – gag, pol, env
• Gag gene – Encodes matrix and coat proteins (p24). Helps protect the viral genome
• Pol gene – Encodes RT, RNase H, Helicase, Integrase. RT (reverse transcriptase) converts RNA into DNA
• Env gene – Encodes spike proteins – gp120, gp41 in lipid envelope
• Repetitive sequences at each end and unique sequences enable DNA copy for integration
• Genome has enhancer sequences allowing for elevated transcription of genes downstream
• 5’ end has U5 sequence while 3’ end has U3 sequence. U5 is the primer binding site while U3 is the promoter enhancer sequence that controls viral replication from 5’LTR.
• Sometimes hijack oncogenes from host genome that encode proteins capable of inducing cancer
• Proviral DNA is integrated randomly into host DNA leading to :-
  • Insertional activation of c-onc, when viral promoters or enhancers cause hyper expression of genes or expression at inappropriate times
  • Insertional inactivation of cellular tumour suppressor genes
  • Insertion of v-onc – activated, transcribed giving oncogenic product
• Transcribed by host RNA pol II and translated by host ribosomes

Continued to Part 2