Assignment Topic :

Factors controlling growth and oncogenesis

Submitted to: Sir Rafique Bhatti

Submitted by : Irsa Shabbir

Roll no : 20044

Subject : Development biology

BS Zoology 6th Semester

Govt. Graduate College
Shakargarh
Growth and oncogenesis:
The processes of cellular proliferation and progressive acquisition of a
specialised phenotype show a remarkable degree of coordination that involves both
intracellular programming and intercellular communication. One of the major incentives for
studying factors that regulate the processes of cellular proliferation and differentiation is the
recognition of their potential contribution to tumorigenesis. In normal cells, stimulatory and
inhibitory events are believed to be under the control of growth factors and growth inhibitory
factors, which are known to be proto-oncogene products. Growth regulatory mechanisms
usually involve the binding of a growth factor to a specific receptor on the cell surface, which
then through an intracellular biochemical cascade leads to cell division. The cell regulation
pathways initiated by growth factors may be subverted at several distinct levels in cancer
cells. Studies of oncogenes have shown that they may function as abnormal growth factors
or abnormal receptors, induce expression of potential signal regulators or encode proteins
which modulate gene transcription. The purpose of the present paper is to examine the role
of growth factors, growth factor receptors and intracellular proteins involved in signal
transduction (with particular regard to the epidermal growth factor receptor system) in the
control of normal growth and differentiation, and their contribution to transformation and
tumorigenesis. We also review the classical theories of neoplasia and various other models.
Chemical carcinogenesis and Vogelstein-Lane model are presented.

Factors controlling growth and

oncogenesis
Oncogenesis:
Oncogenesis is also called tumorigenesis or carcinogenesis.

Oncogenesis means Tumour or mass formation, Is the formation of cancer whereby normal
cells are transformed into cancer cells. The process is characterised by changes at cellular,
genetic and epigenetic levels and abnormal cell division.

Cell cycle checkpoints

There are many check points in a cell cycle which regulates the growth processes in a cell.

• It prevents entry into the next phase of cell cycle.

• It is also called DNA damage checkpoints.

Oncogene
An oncogene is a gene that has the potential to cause cancer or tumour. All are involved in
cancer and uncontrolled cellular growth.

• About 100 different oncogenes have been identified.

• Can be various kinds of proteins. such as Growth factors regulatory genes involved in
control of cell multiplication.

Activation of oncogene
Mutations that occur among proto-oncogenes, which can be termed as normal genes, lead
to the activation of oncogenes.

• In a general sense, proto-oncogenes aid in the differentiation and growth regulation in cells
by coding for proteins as well as in signal transduction. Once activated, a proto-oncogene
becomes an oncogene.

• Upon oncogene activation, the cell multiplies and grows out of control and causes cancer.

Causes of oncogenesis:

Genome instability.

DNA variability or damage.

Genetic factors.

Contribution of field defects.

Epigenetic reasons.
1-Genome instability:

It refers to a high frequency mutation within the genome of cellular lineage.

These mutations can include changes in nucleic acid sequences, within the genome of
chromosomal rearrangements or aneuploidy.

Genome instability may result from failures at different steps of the DNA cycle, from
replication to segregation.

2-DNA Damage:

• DNA damage is a change in the basic structure of DNA that is not itself replicated when the
DNA is replicated.

A DNA damage can be a chemical addition or disruption to a base of DNA or a break in one
or both chains of the DNA strands.

3-Genetic and epigenetic factors:

It includes changes in the nucleotide sequence of the genomic sequence.

Epigenetics involves genetic control by factors other than an individual's DNA sequence.

Epigenetic changes can switch genes on or off and determine which proteins are
transcribed.

Epigenetics is involved in many normal cellular processes.

4-Contribution of Field Defects:

• A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise.

Recent research indicates that cells within a field defect characteristically have an increased
frequency of epigenetic alterations and these may be fundamentally important as underlying
factors in progression to cancer.
Factors controlling Growth, oncogenesis:

There are five kinds of factors that are classified on the basis of the functional and
biochemical properties of protein products of their normal counterparts (proto-oncogenes).
These are

●​ Growth factors
●​
●​ Growth factor receptors
●​
●​ Signal transducers
●​
●​ Transcription factors
●​
●​ Programmed cell death regulators.

1-Growth Factors:

A growth factor is an occurring substance capable of stimulating cell proliferation and cellular
differentiation. Target cells must possess a specific receptor in order to respond to a specific
type of growth factor

Usually it is secreted as Protein, or a Steroid hormone.

Growth factors are important for regulating a variety of cellular processes.

2- Growth factor Receptor:

Growth factor receptors are molecular machines that transmit information in a unidirectional
fashion across the cell membrane

Growth factor receptors are collectively as they have characteristic protein structure
consisting of three principal domains:

(1) the extracellular ligand-binding domain.

(2) the transmembrane domain.

(3) the intracellular tyrosine kinase catalytic domain,

3-Contribution of Field Defects

A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise.

Recent research indicates that cells within a field defect characteristically have an increased
frequency of epigenetic alterations and these may be fundamentally important as underlying
factors in progression to cancer.

4- Signal Transducers:

• Mitogenic signals are transmitted from growth factor receptors on the cell surface to the cell
nucleus through a series of complex interlocking pathways collectively referred to as the
signal transduction cascade.

• Signal transducers are often converted to oncogenes by mutations that lead to their
unregulated activity, which in turn leads to uncontrolled cellular proliferation.
5-Programmed Cell Death Regulation:

• Normal tissues exhibit a regulated balance between cell proliferation and cell death.
Programmed cell death is an important component in the processes of normal
embryogenesis and organ development. A distinctive type of programmed cell death, called
apoptosis.

This process is characterised morphologically by condensation of the cell nucleus, and

cleavage of genomic DNA.

Summary
●​ Two classes of genes, oncogenes and tumour suppressor genes, link cell cycle
control to tumour formation and development. Oncogenes in their proto-oncogene
state drive the cell cycle forward, allowing cells to proceed from one cell cycle stage
the next.

●​ This highly regulated process becomes due to activating genetic gene genetic
alterations that lead to cellular transformation. Tumour suppressor genes, the other
hand, restrict cell cycle progression. Their control over cell division is lost with genetic
alterations leading to their inactivation and as a result it causes cancer or tumour.