Different diseases – from the same gene complex?
Researchers from Harvard University (Boston, Massachusetts), working under the leadership of Kevin Struhl, have shown that cancer, atherosclerosis, diabetes and many other diseases are characterized by a change in the expression of the same gene complex. This indicates the involvement of the same violations of biological mechanisms in the development of a wide range of diseases. The authors of the work, the results of which were published in the April issue of the journal Cancer Cell in the article "A Transcriptional Signature and Common Gene Networks Link Cancer with Lipid Metabolism and Diverse Human Diseases", believe that the genetic relationship they identified indicates the potential use of drugs used in the treatment of metabolic syndrome, cardiovascular and other common diseases, for the treatment of cancer.
The scientists compared the gene transcription profiles of two genetically identical lines of human breast epithelial cells isolated from the same woman's tissue. The cells of one of these lines had a normal phenotype, while the cells of the second line underwent artificially induced malignant degeneration. After that, they conducted a similar experiment with human fibroblast lines. As a result of comparing the results obtained, they identified 343 genes expressed differently in both models and representing a complex of genes typical of malignant tumors.
According to Strul, obtaining similar results became possible thanks to the use of two models. Analysis of one model reveals thousands of genes whose expression differs in cancer and normal cells, while comparing the results of studying two models reduces this list by an order of magnitude.
The authors analyzed the resulting list of genes using bioinformatics methods and identified several families of transcription factors involved in the development of inflammatory reactions and metabolic disorders. Moreover, a study of the literature data showed that many of the identified 343 genes had previously been shown to be involved in the development of diabetes, obesity, heart disease and other diseases that significantly contribute to human mortality.
For a more detailed study of the role of genes involved in the regulation of metabolism, but not previously seen in the development of cancer, the authors selectively knocked them out in cells before the subsequent induction of malignant transformation. It turned out that seven of the eleven tested genes played an important role in the malignancy of both cell types. The results of additional experiments showed that low-density lipoprotein (LDL) and its receptor, which play an important role in the pathogenesis of atherosclerosis, are also involved in the development of cancer.
Based on the results obtained, the researchers formulated a hypothesis according to which the development of many different diseases is based on similar molecular mechanisms. Actually, the idea is that there is a single status of a "sick cell", the phenotype of which and the resulting disease depend on the type of tissue to which the cell belongs.
To test their hypothesis, the authors analyzed the effects of drugs used to treat various diseases, including diabetes – metformin (metformin), arthritis – celecoxib (celecoxib) and atherosclerosis – simvastatin (simvastatin), on malignant cells. Eleven of the thirteen drugs tested suppressed the growth of cancer cell lines.
Experts believe that the results obtained are of great value and indicate the expediency of including such drugs in the protocols of antitumor therapy.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Top killers share genes.
16.04.2010