Telomerase Activity in HL-60 Cells After Treatment with Differentiating Agents.
- Author:
In Ho KIM
1
;
Sook Ja KIM
;
Hee Jeong CHEONG
;
Sung Kyu PARK
;
Gyu Taeg LEE
;
Jong Ho WON
;
Won Suk SUH
;
Seung Ho BAICK
;
Dae Sik HONG
;
Hee Sook PARK
Author Information
1. Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Telomerase activity;
HL-60 cells;
Differentiating agents
- MeSH:
Apoptosis;
Cholecalciferol;
Cytarabine;
DNA;
Embryonic Structures;
Germ Cells;
Granulocytes;
HL-60 Cells*;
Humans;
Monocytes;
Ribonucleoproteins;
Telomerase*;
Telomere;
Tretinoin
- From:Korean Journal of Hematology
1999;34(1):107-117
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Telomeres are repetitive DNA fragments at the termini of chromosomes functioning as stabilizing elements of the DNA. A ribonucleoprotein polymerase, called telomerase, is responsible for the synthesis of such telomeric repeats in embryo and germ cells. During ontogenesis of most normal human somatic cells, there exists a physiological telomerase repressing mechanism. In contrast, malignant cells are characterized by an unlimited progressive potential. Certain physiological agents, such as all-trans retinoic acid (ATRA), 13-cis retinoic acid (13-cisRA), 1alpha-25 dihydroxy vitamin D3 (VD3) and cytosine arabinoside (Ara-C), promote further differentiation of leukemic cells into mature granulocytes and monocytes and subsequently undergo apoptosis. METHODS: To determine if a potential linkage is present between telomerase regulation and the differentiation of malignant hematopoietic cells, the changes in telomerase activity during the maturation of HL-60 cells induced by ATRA, 13-cisRA, VD3 and Ara-C were investigated. RESULTS: Differentiating agents induce HL-60 cells to differentiate into CD11b+ granulocytes and monocyte/macrophages, respectively. Approximately 98% of HL-60 cells acquired the expression of CD11b+ antigen after ATRA, 13-cisRA or Ara-C treatment for 5 days. After 1 day treatment with differentiating agents, no significant difference in telomerase activity was shown between untreated and treated HL-60 cells. A dramatic inhibition of telomerase activity occurred at 3 days treatment of ATRA compared to untreated HL-60 cells. Longer treatment for 5 days with differentiating agents resulted in further decrease of telomerase activity. However, telomerase activity in HL-60 cells was decreased slightly by the VD3 or Ara-C treatment, even though for 5 days. No evidence of differentiation and slight decrease of telomerase activity were observed in ATRA-treated K-562 cells for 5 days. These decrease of telomerase activity were dependent on the incubation time and dose. CONCLUSION: These data clearly show the role of telomerase activity during the differentiation of HL-60 cells. This in vitro model can be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.
