Chromosomal translocation and extra chromosomes help create abnormally high activity of certain proto-oncogenes, which caused by these genetic abnormalities and include those encoding c-myc, HRAS, and vav. The activity of proto-oncogenes is not the only cellular function that is affected; tumour suppressor genes are affected by the chromosomal changes induced by mycoplasma, as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation. Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes. Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of Mycoplasma. A major feature that differentiates mycoplasmas from other carcinogenic pathogens is that the mycoplasmas do not cause the cellular changes by insertion of their own genetic material into the host cell. The exact mechanism by which the bacterium causes the changes is not yet known. Partial reversibility of malignant transformationsThe malignant transformation induced by Mycoplasma species is also different from that caused by other pathogens in that the process is reversible. The state of reversal is, however, only possible up to a certain point during the infection. The window of time when reversibility is possible varies greatly; it depends primarily on the Mycoplasma involved. In the case of M. fermentans, the transformation is reversible until around week 11 of infection and starts to become irreversible between weeks 11 and 18. If the bacteria are killed using antibiotics (i.e.
ciprofloxacin or Clarithromycin) before the irreversible stage, the infected cells should return to normal. Connections to cancer in vivo and future research
Epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. M. genitalium and M. hyorhinis induce malignant phenotype in benign human prostate cells (BPH-1) that were not tumorigenic after 19 weeks of exposure. Types of cancer associated with Mycoplasma
Colon cancer: In a study to understand the effects of Mycoplasma contamination on the quality of cultured human colon cancer cells, a positive correlation was found between the number of M. hyorhinis cells present in the sample and the percentage of CD133-positive cells (a glycoprotein with an unknown function).Gastric cancer: Strong evidence indicates the infection of M. hyorhinis contributes to the development of cancer within the stomach and increases the likelihood of malignant cancer cell development.Lung cancer: Studies on lung cancer have supported the belief that more than a coincidental positive correlation exists between the appearance of Mycoplasma strains in patients and the infection with tumorigenesis.Prostate cancer: p37, a protein encoded for by M. hyorhinis, has been found to promote the invasiveness of prostate cancer cells. The protein also causes the growth, morphology, and gene expression of the cells to change, causing them to become a more aggressive phenotype.Renal cancer: Patients with renal cell carcinoma (RCC) exhibited a significantly high amount of Mycoplasma sp. compared with the healthy control group. This suggests Mycoplasma may play a role in the development of RCC.