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  • Original Paper
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Regulation of prothymosin α by estrogen receptor α: molecular mechanisms and relevance in estrogen-mediated breast cell growth

Oncogene volume 21, pages 5233–5244 (2002)Cite this article

An Erratum to this article was published on 19 November 2002

Abstract

Prothymosin α (PTα) is a small highly acidic protein found in the nuclei of virtually all mammalian tissues. Its high conservation in mammals and wide tissue distribution suggest an essential biological role. While the exact mechanism of action of PTα remains elusive, the one constant has been its relationship with the proliferative state of the cell and its requirement for cellular growth and survival. Recently PTα was found to promote transcriptional activity by sequestering the anticoactivator, REA from the Estrogen Receptor (ER) complex. We now report that Estradiol (E2) upregulates PTα mRNA and protein expression. Further studies indicate that ERα regulates PTα gene transcriptional activity. We have also delimited the region of PTα gene promoter involved in ERα-mediated transcriptional regulation and identified a novel ERα-binding element. Increased intracellular PTα expression in the presence of estrogens is accompanied by increased nuclear/decreased cytoplasmic localization. Increased nuclear expression of PTα is correlated with increased proliferation as measured by expression of Ki67 nuclear antigen. Conversely, inhibition of nuclear PTα expression in breast cancer cells using antisense methodology resulted in the inhibition of E2-induced breast cancer cell proliferation. Overall these studies underscore the importance of PTα in estrogen-induced breast cell proliferation.

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Abbreviations

PTα:

prothymosin α

ERα:

Estrogen Receptor α

E2:

estradiol

TOT:

trans-hydroxytamoxifen

ERE:

estrogen response element

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  1. Department of Pharmacology, Case Western Reserve University, Cleveland, 44122, Ohio, OH, USA

    Nicole R Bianco & Monica M Montano

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  1. Nicole R Bianco
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  2. Monica M Montano
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Correspondence to Monica M Montano.

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Bianco, N., Montano, M. Regulation of prothymosin α by estrogen receptor α: molecular mechanisms and relevance in estrogen-mediated breast cell growth. Oncogene 21, 5233–5244 (2002). https://doi.org/10.1038/sj.onc.1205645

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