Correlation of the ability of retinoids to inhibit promoter-induced anchorage-independent growth of JB6 mouse epidermal cells with their activation of retinoic acid receptor gamma.

Correlation of the ability of retinoids to inhibit promoter-induced anchorage-independent growth of JB6 mouse epidermal cells with their activation of retinoic acid receptor gamma.
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类视黄醇抑制 JB6 小鼠表皮细胞启动子诱导的贴壁独立生长的能力与其视黄酸受体 γ 激活的相关性。

DOI:
10.1016/0304-3835(93)90186-d
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发表时间:
1993
期刊:
影响因子:
9.7
通讯作者:
Dawson,MI
Dawson,MI
中科院分区:
医学1区
文献类型:
--
作者:
Rudd,CJ;Mansbridge,JN;Suing,KD;Dawson,MI

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类维甲酸抑制肿瘤启动子12- o - tetradecanoylphorol -13-acetate (TPA)对小鼠表皮细胞的生物学效应。在表皮中已经发现了特异性的核维甲酸受体(RARs),但介导类维甲酸抑制反应的特异性受体尚未确定。采用JB6小鼠表皮细胞系对维甲酸和6种构象限制性类维甲酸进行体外生物测定。然后将这些活性与这些类视黄醇激活RARs的能力进行比较,在瞬时转染试验中进行转录激活,以确定参与抑制tpa诱导的非锚定生长的类视黄醇受体。类维生素a抑制tpa诱导的JB6细胞在半固体培养基中的集落形成,其浓度对附着细胞的集落形成没有毒性。这些浓度范围从小于10−9-10−6M。4-(5,6,7,8-四氢-5,5,8,8-四甲基蒽-2-基)苯甲酸(TTAB)的效价最高,ec50为0.8 nM。RARα和RARγ在JB6细胞中均有表达。聚合酶链反应法在这些细胞中未检测到RARβ的表达,这与RARβ在小鼠皮肤中的极低水平一致。这些类维生素a对JB6细胞TPA反应的抑制仅与RARγ的转录激活相关,而与RARα的转录激活无关。这些结果表明RARγ很可能是介导类维甲酸在小鼠表皮中的化学预防作用的受体。
Retinoids inhibit the biological effects induced in mouse epidermal cells by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Specific nuclear retinoic acid receptors (RARs) have been indentified in the epidermis, but the specific receptor that mediates the inhibitory response by retinoids is not established. Retinoic acid and six conformationally restricted retinoids were evaluated in an in vitro bioassay using the JB6 mouse epidermal cell line. These activities were then compared with the ability of these retinoids to activate the RARs in transient transfection assays for transcriptional activation to identify the retinoid receptor involved in inhibiting TPA-induced anchorage-independent growth. The retinoids inhibited TPA-induced colony formation of JB6 cells in semisolid medium at concentrations that were not toxic based on colony formation of attached cells. These concentrations ranged from less than 10−9–10−6M. 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylanthracen-2-yl)benzoic acid (TTAB) was the most potent retinoid, with an EC50of 0.8 nM. Both RARα and RARγ were expressed in JB6 cells. Expression of RARβ was not detected in these cells using a polymerase chain reaction assay, consistent with its extremely low level in mouse skin. Inhibition of the TPA response by these retinoids in JB6 cells correlated only with their transcriptional activation of RARγ, but not with that of RARα. These results suggest that RARγ is most probably the receptor that mediates the chemopreventive effects of retinoids in mouse epidermis.
视黄酸受体γ基因的基因组结构。
DOI: 10.1093/nar/19.3.573
发表时间: 1991
影响因子: 14.9
作者:
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DOI: --
发表时间: 1981
影响因子: 5.2
作者:
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影响因子: 11.1
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DOI: 10.1002/j.1460-2075.1991.tb07922.x
发表时间: 1991-01-01
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
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DOI: --
发表时间: 1991
期刊: Cancer research
影响因子: 11.2
作者:
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通讯作者: Pfahl,M