CARCINOGENESIS

Four possible explanations for malignant transformation.

1. Viruses 2. Cell mutation 3. cell mis-differentiation 4. Physical/environmental effects (x-rays/asbestos)

Carcinogenisis

Carcinogenisis is the process of producing or causing a cancer. Two factors involved in carcinogenesis are environment and heredity.

Chemical carcinogens

Chemical carcinogens fall into two groups: genotoxic and epigenetic.

DNA repair genes

DNA repair genes ensure that each strand of genetic information is accurately copied during cell division in the cell cycle. Mutations in these genes lead to an increase in the frequency of other mutations.

Initiation

Initiation is the transformation of a normal cell to a pre-malignant one.

Essential steps to cancer causation and development:

1. The production of altering DNA in the cell by attack from a reactive form of a carcinogen. 2. The translocation and amplification of proto-oncogenes.

Colon can er proto-oncogenes

1. Colon cancer is usually assoiated with the activation of oncogenes and the deletion of tumor suppressor genes.

Oncogenes are produced by

1. DNA breaks and translocations. A chromosome breaks off and translatesnto a specific location on another chromosome making a specific kind of cancer. 2. Double-dose effect. A back-up chromosome starts telling the cell to make proteins at the same time as the primary chromosome is telling it to make that protein. Therefore the cell makes twice as much of this protien, which in turn produces a malignant transformation.

Brast cancer protp-oncogenes

1. HER-2 neu is a cancer related protein. Over-expression of this protein is assiciated with a poor prognosis. 2. Epidermal Growth Factor Receptor (EGFR) is associated with larger tumors. Patients with large amounts of EGFR have a less favorable prognosis than those with smaal amountsmof this receptor. 3. P-53 is a protien that is usually elevated with elevated ER/PR (estrogen and progesterone receptors). It is an indicator of whether or not the ER function is working.

Carcinogen

A carcinogen is any cancer-producing substance or organism.

Mutagen

A mutagen is an agent that induces genetic mutation.

Oncogenic agent

An oncogenic agent is anything that causes cancer, or is suitable for the formation and development of neoplasms.

Cancer genes

Cancer genes are either oncogenes or tumor suppressor genes.

Carcinogenesis

Carcinogenesis occurs through a number of successive steps that are essential for the development of a clinically invasive cancer.

Epigenetic agents (promoters)

Epigenetic agents (also called promoters) produce other biological effects such as accelerated cell cycles and hormonal imbalances. Promoters cannot cause cancer without a prior cell change. The action of promoters requires their presence in high levels for a long period of time. The effects of promoters are reversible. Examples of promoters: bile acids and colon cancer. Saccharin and bladder cancer.

Genotoxic carcinogens

Genotoxic carcinogens alter DNA and are mutagenic. Almost all human carcinogens are genotoxic.

Oncogenes

Oncogenes are normal host genes conserved in evolution (probably because they are for growth and repair) that, when activated by an outside factor, speed up the changes and replication of a cancerous cell.

Promotion

Promotion is a process occuring after initiation that stimulates proliferation of the initiated cell line.

Proto-oncogenes

Proto-oncogenes are normal genes that control the production of protiens that are involved in the control of the cell cycle. Mutations in these genes are caused either by chance or attack by certain carcinogens and result in an overproduction of the protein that may stimulate cellular division. This increasedmcellular division may result in the development of neoplasia or malignancy. The activated form of the gene is an oncogene.

Tumor suppressor genes

Tumor suppressor genes normally "put the brakes" on oncogenes. When mutations deactivate or eliminate these control genes , precancerous cells are free to develop and spread.