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Cloning and characterization of a novel steroid hormone responsive gene

Estrogen modulates growth and function of female reproductive tissues, such as uterus and mammary gland, by eliciting an array of biochemical responses and is linked to mammary carcinogenesis. To further understand the involvement of estrogens in complex physiological processes, we sought to increase the spectrum of genes regulated by estrogens. We cloned a novel 3.719 Kb cDNA from rat uterine tissue, termed steroid sensitive gene-1 (SSG1), encoding a nuclear protein of 386 amino acids and demonstrated that it is regulated by 17beta-estradiol in the uterus and mammary gland. In the rat uterus, SSG1 mRNA is down-regulated by 17beta-estradiol in time- and dose-dependent manners. In the mammary gland, chronic 17beta-estradiol treatment resulted in a significant accumulation of the SSG1 protein, which was dependent on the presence of elevated levels of 17beta-estradiol. SSG1 was consistently over-expressed in estrogen-dependent 7,12-dimethylben(a)anthracene-induced rat mammary tumors which may be a consequence of an altered hormonal environment. In rat and human mammary tissue, SSG1 protein was localized to the myoepithelial cells of the mammary ducts and to the smooth muscle cells of the vasculature. In human mammary tumors SSG1 was predominant in the epithelial compartment. In males, we demonstrate that SSG1 protein expression, immunolocalized to the prostatic smooth muscle cells and to the smooth muscle cells of the vasculature, is dependent on the presence of androgens. We conclude that SSG1 expression is regulated by steroid hormones in both female and male reproductive systems. We propose that SSG1 is a target for both estrogen and androgen modulation and that it may be implicated in estrogen functions related to mammary carcinogenesis.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.37773
Date January 2000
CreatorsMarcantonio, Daniela.
ContributorsAlaoui-Jamali, Moulay (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageDoctor of Philosophy (Division of Experimental Medicine.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001804652, proquestno: NQ70090, Theses scanned by UMI/ProQuest.

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