The Roles of Nucleophosmin/B23 in Cellular Mortalization

  • Yung, Benjamin Yat-Ming (PI)

Project: Ministry of Health and WelfareMinistry of Health and Welfare Commission Research

Project Details

Abstract

The overall aim of this project is to define the control over the regulation of cell growth, apoptosis and differentiation. Long-term objectives that may accrue from these studies are the developments of new and better understanding of the forces guiding normal and cancer cell differentiation and death. The mechanism of growth control is one of the most important and least understood areas in biology. Tumors are usually recognized by the fact that the cells have shown abnormal growth. Tumor cells differ from normal cells in that they are no longer responsive to normal growth controlling mechanisms. Current chemotherapeutic drugs act for the most part by killing cancer cells directly. Recently, however, researchers have begun clinical trials of several agents that act instead by changing the biological properties of cancer cells so that they lose one of the major characteristics, namely, the ability to divide continuously. The new work on tumor differentiation and apoptosis aims to shift the balance back again, thereby removing the potential for uncontrolled growth from the tumor cells. The studies of the processes of growth, apoptosis and differentiation in this project will be carried out in tumor cells (cultured cells & tissue samples from cancer patients). One important difference between cancer and normal cells is hyperactivity and pleomorphism of the nucleoli. The nucleolus in cancer cells undergoes extreme variations in size, shape, fine structure, and cytochemical composition. Our recent findings demonstrate that nucleophosmin/B23 is transcriptionally down-regulated during retinoic acid (RA) induced cellular differentiation and sodium butyrate (BuONa) induced apoptosis of HL-60 promyelocytic leukemia cells. The potentiation of RA-induced differentiation and BuONa-induced apoptosis by nucleophosmin/B23 antisense oligomer further implicates that nucleophosmin/B23 plays an important role in the down regulation of nucleolar function for cellular differentiation and apoptosis. Whether the decrease of nucleophosmin/B23 mRNA as a result of antisense treatment would render tumor cells more susceptible to chemotherapeutics or induction of differentiation or apoptosis becomes an important question to be addressed. We hypothesize that the induction of cellular differentiation or apoptosis is associated with down-regulation of nucleophosmin/B23. Down-regulation of nucleophosmin/B23 may be one of the important steps for blocking the "normal" cells from becoming "abnormal' or a step towards making immortal cancer cells mortal. Nucleophosmin/B23 could be importantly related to telomerase. Attempts will thus be made in the present study to determine the biological roles of nucleophosmin/B23 in regulation of cell mortalization, growth, differentiation and apoptosis.

Project IDs

Project ID:PG9102-0359
External Project ID:NHRI-EX90-8935SL
StatusFinished
Effective start/end date01/01/0131/12/01

Keywords

  • Nucleolar protein
  • differentiation
  • apoptosis

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.