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Cancer - facts
Cancer is a genetic disease It is caused by mutation that predominantly occur in somatic cells and only 1% of cancers are associated with germ-line mutations Arise from single mutation and results from accumulation of mutations
Table 20.1
What is cancer?
Clinically cancer is defined as a large number (up to a hundred) of complex diseases that behave differently depending on the cell types from which they originate All cancer cells share two fundamental properties : * Cell proliferation * Metastasis
Contd.
Unregulated cell proliferation, characterized by abnormal cell growth and division Metastasis, a process that allows cancer cells to spread and invade other parts of the body Genes for regulation of above two processes were either mutated or expressed inappropriately in cancer cells
Contd.
When a cell simply loses genetic control over its growth and division, it may give rise to a multicellular mass, a benign tumor If the cells in tumor also acquire the ability to break loose, enter the bloodstream, invade other tissues, and form secondary tumors elsewhere in the body, they become malignant
A single mutation is not sufficient to transform a normal cell into a tumor-forming, malignant cell The rate of mutation and age related cancer proves that cancer develops from the accumulation of several mutagenic events in a single cell Another indication is the delay that occurs between exposure to carcinogens and the appearance of cancer Also they develop in progressive steps from mildly aberrant and progressing to cells that
The high level of genomic instability seen in cancer cells is known as mutator phenotype Genomic instability is characterized by the presence of gross defects such as translocations, aneuploidy, chromosome loss and deletions Often they show specific chromosomal defects that are used to diagnose the type and stage of cancer
Figure 20.2
Examples
Xeroderma pigmentosum (XP) is a rare hereditary disorder that is characterized by extreme sensitivity to ultraviolet light and other carcinogens. People are defective in nucleotide excision repair, with mutations appearing in any one of seven genes whose products are necessary to carry out DNA repair HNPCC is an autosomal dominant syndrome and lead to development of colorectal and other cancers
Epigenetics is the study of factors that affect gene expression in a heritable way but that do not alter the nucleotide sequence of DNA DNA methylation and histone modifications such as acetylation and phosphorylation are examples The genomic pattern and the locations are inherited There is much less DNA methylation in cancer cells than in normal cells. At the same time, the promoters of some genes are
G1 cell prepares for DNA synthesis S cells chromosomal DNA is replicated G2 cell continues to grow and prepare for division M duplicated chromosomes condense, sister chromosomes separate to opposite poles and cell divides into two If the cell receives signals to stop growing, it enters the G0 phase of cell cycle
Figure 20.5
During G0, the cell remains metabolically active but does not grow or divide Cancer cells are unable to enter G0 phase and instead, they continuously cycle Their rate of proliferation is not high but it cant stop cell cycle The process of transmitting growth signals from the external environment to the cell nucleus is known as signal transduction
There are at least three distinct points in the cell cycle at which the cell monitors external signals and internal equilibrium before proceeding to next stage G1/S cell monitors its size and determines whether its DNA has been damaged G2/M physiological conditions in the cell are monitored prior to mitosis M attachment spindle fibers to the centromeres are monitored
Figure 20.6
Cell also controls cell cycle by means of two classes of proteins: cyclins and cyclindependent kinases CDK/cyclin complex then selectively bring about changes necessary to advance the cell through the cell cycle Cell cycle is regulated by interplay of genes whose products either promote or suppress cell division
Figure 20.7
Control of apoptosis
If DNA or chromosomal damage is so severe that repair is impossible, the cell may initiate a second line of defense-a process called apoptosis or programmed cell death The nuclear DNA becomes fragmented, internal cellular structures are disrupted, and the cell dissolves into small spherical structures known as apoptotic bodies Finally these bodies are engulfed by immune systems phagocytic cells The same genes controlling checkpoints, controls apoptosis
p53 activates transcription of BAX and blocks cl2, which promotes apoptosis.
Figure 20.8
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