Bcl-X-L expression and its downregulation by a novel retinoid in breast carcinoma cells

被引:27
作者
Hsu, CKA
Rishi, AK
Li, XS
Dawson, MI
Reichert, U
Shroot, B
Fontana, JA
机构
[1] UNIV MARYLAND, DIV HEMATOL & MED ONCOL, DEPT MED, CTR CANC, BALTIMORE, MD 21201 USA
[2] UNIV MARYLAND, BALTIMORE VET AFFAIRS MED CTR, BALTIMORE, MD 21201 USA
[3] SRI INT, DIV LIFE SCI, MENLO PK, CA 94025 USA
[4] CTR INT RESCHERCHES DERMATOL, GALDERMA, CIRD, VALBONNE, FRANCE
关键词
D O I
10.1006/excr.1997.3509
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have recently found a novel retinoid, 6-[3-(1-adamantyl) -4-hydroxphenyl]-2-naphthalene carboxylic acid (CD437), which induces G(1) cell cycle arrest and apoptosis in human breast carcinoma (HBC) cells (Oncogene 11, 493-504, 1995). CD437 downregulates the expression of a number of proteins which antagonize apoptosis. bcl-X-L, a homologue of bcl-2, antagonizes apoptosis, while bcl-X-S enhances apoptosis. We have found that estrogen receptor (ER)-negative HBCs express higher levels of bcl-X-L and significantly lower levels of bcl-2 than their ER-positive counterparts. Neither cell type expresses bcl-X-S. The addition of CD437 (1 mu M) results in a fourfold downregulation of bcl-X-L mRNA and protein levels followed by apoptosis in MDA-MB-231 and MDA-MB-468 cells. CD437 concentrations as low as 10 nM cause a significant reduction in both bcl-X mRNA and bcl-X-L protein expression. CD437-dependent downregulation of bcl-X mRNA and bcl-X-L protein expression occurs within 24 h of CD437 addition to the cells. Retinoic acid does not effect bcl-X mRNA or bcl-X-L protein expression. CD437 is a potent inducer of apoptosis in a number of breast carcinoma cells lines and downregulates the expression of a number of proteins which antagonize apoptosis. (C) 1997 Academic Press.
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页码:17 / 24
页数:8
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