Study on Growth Suppression Effect of Vetamin D3 Mediated by Transfrorming Growth Factor-B1(TGF-B1) in Acute Myelogenous Leukemic Cell.
- Author:
Chul Won JUNG
1
;
Sang Jae LEE
;
Myung Joo AHN
;
Tae Joon JUNG
;
In Soon KIM
;
Il Young CHOI
;
Jae Koo SEOL
;
Eun Sil KIM
;
Byung Kook KIM
;
Young Yeol LEE
Author Information
1. Department of Internal Medicine, College of Medicine, Chung-Ang University.
- Publication Type:Original Article
- Keywords:
Vitamin D;
EB1089;
Acute myelogenous leukemia;
TGF-B1
- MeSH:
Antibodies, Neutralizing;
Blotting, Northern;
Cell Line;
Cholecalciferol;
DNA;
Immunoenzyme Techniques;
Leukemia, Myeloid, Acute;
RNA, Messenger;
Vitamin D
- From:Journal of the Korean Cancer Association
1998;30(4):827-841
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Vitamin D3 was shown to arrest the growth of acute myelogenous leukemic cells and transforming growth factor- B1 (TGF- B1) was reported to be involved in the mechanism of vitamin D3. We studied the growth inhibitory effect of 1,25(OH)2-vitamin D3(C) and its analogue (EB1089) in leukemic cell lines and the changes in the secretion or the activation of TGF-B1 in the supernatant and the status of TGF-B1 type II receptor. MATERIALS AND METHODS: Growth inhibition by vitamin D3 and TGF-B1 in 5 leukemic cell lines (HEL, HL-60, U937, KG-1, K562) were assessed with clonogenic and [3H]thymidine assay respectively. TGF-B type II receptor status was examined by Southern and Northern blotting. The concentrations of TGF- B1 in the supernatant were quantitated by enzyme immunoassay. RESULTS: The growth of HEL, HL-60, U937 were inhibited in a dose-dependent fashion by both C and EB1089, more markedly by the latter. Anti-TGF-B neutralizing antibody partially reversed the growth inhibition. TGF-B1 markedly inhibited the growth of HEL, U937, KG-1, SNU-16 dose dependently while HL-60 and K562 showed no growth inhibition. HEL secreted latent TGF- 1 and HL-60 activated latent TGF- B1 or secreted active TGF-B1 irrespective of the treatment with vitamin D3. In U937, vitamin D3 increased the concentration of both active and latent TGF-B1. Deletion or abnormal expression of TGF- B type II receptor gene was not found in the 5 cell lines examined. CONCLUSION: Vitamin D3 has various pattern of growth inhibition in acute myelogenous leukemia and inhibits the growth of some cell lines by secretion or activation of TGF-B1. Abnormality of TGF-B type II receptor DNA or mRNA seems to be rare.
