Bcl-X(L) expression and its downregulation by a novel retinoid in breast carcinoma cells.
Bcl-X(L) expression and its downregulation by a novel retinoid in breast carcinoma cells.
复制标题
乳腺癌细胞中 Bcl-X(L) 的表达及其通过新型视黄醇的下调。
DOI：
10.1006/excr.1997.3509
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Fontana,JA
中科院分区：
文献类型：
--
作者：
Hsu,CK;Rishi,AK;Li,XS;Dawson,MI;Reichert,U;Shroot,B;Fontana,JA
我们最近发现了一种新的类维生素A，6-[3-（1-金刚烷基）-4-羟基苯基]-2-萘甲酸（CD 437），它能诱导人乳腺癌（HBC）细胞的G1期细胞周期停滞和细胞凋亡（Oncogene11，493 - 504，1995）。CD437下调许多拮抗细胞凋亡的蛋白质的表达。bcl-2的同源物bcl-XL可拮抗细胞凋亡，而bcl-XS可促进细胞凋亡。我们发现雌激素受体（ER）阴性的HBCs比ER阳性的HBCs表达更高水平的bcl-X和更低水平的bcl-2。两种细胞类型均不表达bcl-XS。加入CD437（1 μ M）导致MDA-MB-231和MDA-MB-468细胞中bcl-XLmRNA和蛋白水平下调4倍，随后发生凋亡。CD437浓度低至10 nM时，bcl-X mRNA和bcl-XL蛋白表达均显著降低。CD437依赖性的bcl-X mRNA和bcl-XL蛋白表达下调发生在CD437加入细胞后24小时内。维甲酸不影响bcl-X mRNA和bcl-XL蛋白的表达。CD437是许多乳腺癌细胞系中的细胞凋亡的有效诱导剂，并且下调许多拮抗细胞凋亡的蛋白质的表达。
We have recently found a novel retinoid, 6-[3-(1-adamantyl)-4-hydroxphenyl]-2-naphthalenecarboxylic acid (CD437), which induces G1cell cycle arrest and apoptosis in human breast carcinoma (HBC) cells (Oncogene11, 493–504, 1995). CD437 downregulates the expression of a number of proteins which antagonize apoptosis. bcl-XL, a homologue of bcl-2, antagonizes apoptosis, while bcl-XSenhances apoptosis. We have found that estrogen receptor (ER)-negative HBCs express higher levels of bcl-XLand significantly lower levels of bcl-2 than their ER-positive counterparts. Neither cell type expresses bcl-XS. The addition of CD437 (1 μM) results in a fourfold downregulation of bcl-XLmRNA and protein levels followed by apoptosis in MDA-MB-231 and MDA-MB-468 cells. CD437 concentrations as low as 10 nMcause a significant reduction in both bcl-X mRNA and bcl-XLprotein expression. CD437-dependent downregulation of bcl-X mRNA and bcl-XLprotein expression occurs within 24 h of CD437 addition to the cells. Retinoic acid does not effect bcl-X mRNA or bcl-XLprotein 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.