Mechanism of Cell Proliferation—Cell Cycle, Oncogenes, and Senescence

Abstract

Cell proliferation is regulated through a transition between the G0 phase and cell cycle. We isolated a mammalian temperature-sensitive mutant cell line defective in the function from the G0 phase to cell cycle. Senescent human somatic cells fail to enter into the cell cycle from the G0 phase with stimulation by any growth factor. Telomere shortening was found to be a cause of cellular senescence, and reexpression of telomerase immortalized human somatic cells. Immortalized human somatic cells showed normal phenotypes and were useful not only for basic research but also for clinical and appliedˆelds. The importance of p53 and p21 activation/induction i now well accepted in the signal transduction process from telomere shortening to growth arrest, but the precise mechanism is largely unknown as yet. We found that the MAP kinase cascade and histone acetylase have an important role in the signaling process to express p21. Tumor tissues and cells were found to have strong telomerase activity, while most normal somatic human tissues showed very weak or no activity. Telomerase activity was shown to be a good marker for early tumor diagnosis because signiˆcant telomerase activity was detected in very early tumors or even in some precancerous tissues compared with adjacent normal tissues. Telomere/telomerase is a candidate target for cancer chemotherapeutics, and an agent that abrogated telomere functions was found to kill tumor cells eŠectively by inducing apoptosis whereas it showed no eŠect on the viability of normal cells.

HOTAIR‐EZH2 inhibitor AC1Q3QWB upregulates CWF19L1 and enhances cell cycle inhibition of CDK4/6 inhibitor palbociclib in glioma

“…Next, we found that overexpression of this gene can inhibit the proliferation of glioma cells, thereby confirming its inhibitory effect on the proliferation of glioma cells. Furthermore, cell cycle disorders can lead to uncontrolled cell proliferation and ultimately tumorigenesis 27‐29 . A previous literature on HOTAIR and cell cycle reported that the reduction in HOTAIR expression resulted in a significant increase in cells in the G0/G1, and that AQB is a potent blocker of HOTAIR‐EZH2.…”

Establishment and characterization of a new conditionally immortalized human astrocyte cell line

“…Meanwhile, because generally immortalized cells have infinite proliferation ability and differentiation phenotype simultaneously (Ide 2006), cell immortalization techniques offer promising opportunities related to the development of human astrocyte-derived cells that show excellent proliferation in conjunction with stable astrocytic functionalities. Accordingly, it is hoped that human immortalized astrocytes will allow researchers to overcome various limitations imposed on use of primary cells while simultaneously allowing a variety of investigations related to human astrocytes.…”