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Cell Growth & Differentiation Vol. 10, 705-712, October 1999
© 1999 American Association for Cancer Research


Articles

Role of CD14 Expression in the Differentiation-Apoptosis Switch in Human Monocytic Leukemia Cells Treated with 1{alpha},25-Dihydroxyvitamin D3 or Dexamethasone in the Presence of Transforming Growth Factor ß1

Yasuhiro Kanatani, Takashi Kasukabe, Junko Okabe-Kado, Yuri Yamamoto-Yamaguchi, Naokazu Nagata, Kazuo Motoyoshi and Yoshio Honma2

Saitama Cancer Center Research Institute, Ina, Saitama 362-0806 [Y. K., T. K., J. O-K., Y. Y-Y., Y. H.], and Third Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513 [Y. K., N. N., K. M.], Japan

Abstract

Transforming growth factor ß (TGF-ß) enhanced the growth-inhibitory activities of dexamethasone (Dex) and 1{alpha},25-dihydroxyvitamin D3 (VD3) on human monocytoid leukemia U937 cells. TGF-ß and VD3 synergistically increased the expression of differentiation-associated markers such as the CD11b and CD14 antigens, whereas TGF-ß and Dex did not. On the other hand, TGF-ß and Dex synergistically increased the number of Apo2.7-positive cells, which represents the early stage of apoptosis, whereas TGF-ß and VD3 did not, suggesting that TGF-ß enhanced apoptosis with Dex and enhanced monocytic differentiation with VD3. In the presence of TGF-ß, the retinoblastoma susceptibility gene product, pRb, was synergistically dephosphorylated by Dex as well as VD3. TGF similarly enhanced the expression of the p21Waf1 gene in U937 cells treated with Dex and VD3. TGF-ß dose-dependently increased the expression of Bcl-2 and Bad and decreased the expression of Bcl-XL in U937 cells. Dex enhanced the down-regulation of Bcl-XL expression in TGF-ß-treated cells, whereas VD3 blocked this down-regulation of Bcl-XL. However, the down-regulation of Bcl-XL by treatment with the antisense oligomer did not affect the apoptosis or differentiation of U937 cells. The apoptosis of CD14-positive cells was suppressed in the VD3 plus TGF-ß-treated cultures. These results suggest that the expression of CD14 is involved in the survival of differentiated cells.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.