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首页> 外文期刊>The Journal of Steroid Biochemistry and Molecular Biology >Alternative splicing of the estrogen receptor primary transcript normally occurs in estrogen receptor positive tissues and cell lines.
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Alternative splicing of the estrogen receptor primary transcript normally occurs in estrogen receptor positive tissues and cell lines.

机译：雌激素受体初级转录物的选择性剪接通常发生在雌激素受体阳性组织和细胞系中。

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Several laboratories have described estrogen receptor mRNA variants created by skipping internal exons. Some of the putative proteins encoded for by these variants have been functionally characterized by transfection analyses. The variant lacking exon 5 would lead, if translated, to a truncated receptor which shows dominant positive transactivation activity in the absence of hormone. It has been postulated that the variant could account for anti-estrogen resistant tumor growth and for expression of the progesterone receptor in estrogen negative tumors. In order to understand the possible role this and other variants may have in the tumorigenesis of mammary tissue we have carried out a thorough analysis of variants expressed in a tumor cell line (MCF-7), in a tumor sample and in a sample of normal breast tissue derived from mammary reduction surgery. We performed rt-PCR analyses followed by hybridization with exon specific oligonucleotide probes. By these means we have detected nine different variants co-expressed in MCF-7 cells and at least the major variants were equally expressed in normal and neoplastic breast tissue. The same is true for the variant lacking exon 5 which, however, resulted to be a variant of low expression in the three samples analyzed. Variant formation appeared to be restricted to the estrogen receptor messenger since several other members of the superfamily of nuclear receptors did not show variant formation. We also have analyzed the effect of the most abundantly expressed variant, the exon 4 lacking variant, on normal estrogen receptor function, on the growth and on the response to estradiol and to tamoxifen of MCF-7 cells. Although over-expressed at high levels this variant has, if any, only marginal effects on the expression of endogenous estrogen regulated genes and on growth and response to the hormone and its antagonist. Although the lack of function of this variant cannot be extrapolated to other variants, their involvement in tumor formation appears rather unlikely since they are also expressed in normal tissue and the single variant is expressed in addition to many others, some of which might have opposing effects. Variant formation is, however, specific for the estrogen receptor and apparently regulated with tissue specificity as our expression analysis in normal mouse tissues shows. Therefore the variants probably have a physiological significance yet to be discovered.
机译：几个实验室已经描述了通过跳过内部外显子产生的雌激素受体mRNA变异体。这些变体编码的某些推定蛋白质已通过转染分析进行了功能鉴定。缺少外显子5的变体，如果翻译，将导致截短的受体，该受体在缺乏激素的情况下显示出显性的正反式激活活性。推测该变体可以解释抗雌激素抵抗性肿瘤的生长以及孕激素受体在雌激素阴性肿瘤中的表达。为了理解该变体和其他变体在乳腺组织的肿瘤发生中可能发挥的作用，我们已经对肿瘤细胞系（MCF-7），肿瘤样品和正常样品中表达的变体进行了全面分析。乳房组织来源于减少乳房手术。我们进行了rt-PCR分析，然后与外显子特异性寡核苷酸探针杂交。通过这些方法，我们检测到了在MCF-7细胞中共表达的9种不同变体，并且至少主要变体在正常和赘生性乳腺组织中均等表达。对于缺少外显子5的变体也是如此，但是，这导致了在所分析的三个样品中低表达的变体。变体形成似乎仅限于雌激素受体信使，因为核受体超家族的其他几个成员没有显示出变体形成。我们还分析了表达最丰富的变体，缺少外显子4的变体对正常雌激素受体功能，对MCF-7细胞的生长以及对雌二醇和他莫昔芬的反应的影响。尽管在高水平上过表达，但是该变体对内源雌激素调节基因的表达以及对激素及其拮抗剂的生长和应答仅具有边际作用。尽管不能将这种变体的功能缺失推论到其他变体，但它们参与肿瘤形成的可能性似乎很小，因为它们也在正常组织中表达，并且除了许多其他变体之外，还表达了单个变体，其中一些可能具有相反的作用。但是，正如我们在正常小鼠组织中的表达分析所示，变异体的形成对雌激素受体具有特异性，并且显然受到组织特异性的调节。因此，这些变体可能具有尚未发现的生理意义。

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