A research group led by Professor Kyoko Miura of the Institute for Genetic Disease Control, Hokkaido University, and Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine decided to produce iPS cells from "Hadakadebanezumi", which has a long life span and is less prone to cancer. Announced that it was successful for the first time in the world.
The naked mole rat has a long lifespan of about 30 years and is extremely resistant to tumor formation.On the other hand, iPS cells have many similarities to cancer cells, and their tumor-forming ability (teratoma-forming ability) is one of the obstacles to cell transplantation therapy.This study is said to have verified the feasibility of producing iPS cells from the naked mole rat, which is resistant to canceration, and the ability of the produced iPS cells to form tumors.
This time, fibroblasts were produced from the skin of the naked mole rat, and the factors required for reprogramming were introduced into the gene by the same method as in other animals, and iPS cells were successfully produced.In addition, normal iPS cells form tumors when transplanted in an undifferentiated state, but in the case of Hadakadebanezumi iPS cells, tumors are formed by activation of the tumor suppressor gene ARF and deletion of the function of the oncogene ERAS. It became clear that it did not form.
Furthermore, it was found that when ARF is artificially suppressed during the production of naked mole rat iPS cells, cell proliferation is stopped and the state of "cell senescence", which is one of the tumor suppressor mechanisms, is reached.This phenomenon was named "ARF-suppressed cellular senescence (ASIS)".ASIS also occurred when ARF was artificially suppressed under cancerous stress (overexpression of the oncogene cMYC and proliferation stress due to cell culture).
It was found that the naked mole rat has a dual canceration suppression mechanism that ASIS functions under ARF suppression as well as by activation of ARF.In the future, by elucidating the mechanism of cancer resistance of the naked mole rat, it will be useful for human health and longevity and cancer prevention.