Molecular biology of cancer
Techniques in molecular biology have helped in understanding the most intimate structure of the cancer cell. It has been found that at molecular level two mechanisms operate.
1. The parts of genome involved in cell growth become activated. These are called the ' proto-oncogenes'. These strands of DNA induce malignant growth tranformation in the cells. The conversion of proto-oncogenes into oncogenes can happen due to 'point mutations' on DNA. Further such cancer cells display chromosomal abnormalites such as duplication, deletions and transloca-tions. Thus such alterations in gene arrangement can lead to generation of oncogenes.
Oncogenes of human tumours
Oncogene Type of cancer Activation mechanism
hox11 Acute T-cell leukemia Translocation
erbB-2 Breast and ovarian carcinomas Amplification
L-myc Lung carcinoma Amplification
ret Thyroid carcinoma DNA rearrangement.
A distinct mechanism by which oncogenes are activated in human tumors is amplification. It results in elevated gene expression. Gene amplification is very common in cancer cells. It occurs a thousand times more frequently than in normal cells. Molecular biologists are now working on the products of oncogenes.
2. The growth of normal cells is controlled by suppressor genes. In cancer, parts of the genome functioning as the suppressor gene are either lost or inactivated. Hence, negative regulators of cell proliferation are removed. It contributes to the abnormal proliferation of cells.
Gene Type of cancer
APC Colon / rectum carcinoma
BRCA 1 Breast and ovarian carcinoma
1 NK 4 Melanoma, lung carcinoma, brain tumors, leukemias, lymphoma
PTEN Brain tumors, kidney and lung carcinomas.
The protein products of the tumor suppressor genes normally inhibit cell proliferation. Inactivation of such genes therefore leads to tumor development.
The complete sequence of events required for the development of any human cancer is not yet known. But it is clear that both the activation of oncogenesand the inactivation of tumor suppressor genes are critical steps in tumor initiation and progression. Simultaneous effect on both the genes will result in multiple genetic defect. It results in the increased proliferation, invasiveness and metastatic potential of cancer cells.
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