Researchers Investigate Genetic Role of Ribosomes in Cell Proliferation
06/15/00 Portland, Ore.
Researchers at Oregon Health Sciences University are one step closer to understanding life and death at the cellular level. OHSU scientists, along with researchers at three institutions in Switzerland, discovered that the absence of a key gene results in a sudden halt of cell proliferation and a block in the cell cycle. The conclusions of this study are printed in the June 16 edition of the journal Science. Swiss collaborators for the study included researchers from the Friedrich Miescher Institute, the University of Zurich and the University of Basel.
The gene at the center of this research, called S6, is crucial in the production of ribosomes. Ribosomes are cell particles responsible for protein synthesis. To study the role of the S6 gene, scientists at the Friedrich Miescher Institute developed a mutant mouse lacking the S6 gene. OHSU scientists used a different mouse mutant to study the growth of liver cells lacking S6. These mice were transplanted with healthy liver cells containing the S6 gene in their DNA and S6-deficient liver cells. Following transplantation of the two types of liver cells, the animals were closely observed. In contrast to normal liver cells, those that lacked S6 did not produce new ribosomes and did not undergo even a single cell division. This indicates the crucial importance of the S6 gene in controlling the initiation of mitosis, or cell division.
"Liver tissue is one of the few tissues of the body which can regenerate itself," said Eugenio Montini, Ph.D., postdoctoral fellow in the Department of Molecular and Medical Genetics in the School of Medicine at OHSU. "However, we believe without S6, a checkpoint mechanism in the cell detects that something is wrong and regeneration does not occur. Now we must further study this process so that we might use it to combat liver disease and other diseases where cell proliferation stops."
While liver cells without the S6 gene were unable to proliferate, the cells did survive and continue to grow. "Once introduced into the mice, the abnormal liver cells did not suddenly die," said Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics in the School of Medicine at OHSU. "They continued to grow like normal cells. However, these cells were unable to undergo mitosis."
The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, an institute of the National Institutes of Health and is considered an important step in understanding cell death and proliferation in healthy and diseased organs.
"Montini, Grompe and their colleagues have added an important piece to the large and complex puzzle of liver growth and regeneration," said Jay H. Hoofnagle, director of the Division of Digestive Diseases and Nutrition at the NIDDK. "The ribosomal S6 gene is clearly important in the process of normal regeneration of the liver. This work will lead to a better understanding of how the liver heals in response to injury. With such better understanding, better management and therapies for liver diseases are likely to follow."