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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.

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

 

Rb                                 Retinoblastoma

 

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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