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Characterization of Uterine Derived Growth Inhibitor: A Novel Growth Inhibitor of Estrogen Receptor

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Annual rept. 19 May 1998-18 Jun 1999

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We reported the purification of UDGI, a uterine derived growth inhibitor. UDGI protein shares 98 identity to ps20 growth inhibitor isolated from urogenital sinus mesenchymal cells. Although purified UDGI potently inhibited breast cancer cell growth, recombinant UDGI exhibited mild inhibition. UDGI antibody recognized native UDGI from uterine fluid and conditioned media of UDGI-transfectant cells with molecular mass of 24. 27 and 29 kDa. UDGI cDNA was isolated from a rat uterus cDNA library. UDGI transcripts were detected in rat mammary tissue and in various female rat tissues with highest expression in the lung and heart. In vitro, UDGI secretion was reduced by IGF-I, IGF-II, insulin and TGF-alpha. In vivo, UDGI expression was inhibited by estradiol and induced by pure antiestrogen ICI 182780 ICI and tamoxifen. UDGI mRNA was barely detected in mammary tissue of old female rats and in DMBA mammary tumours. Suppression of tumour growth by ICI and tamoxifen was associated with upregulation of UDGI gene expression. Acceleration of apoptosis was observed in stable UDGI-transfectant MCF-7 cell lines following serum starvation. The results suggest that UDGI may function as a mediator of local growth and apoptosis mechanisms.

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  • Biochemistry
  • Medicine and Medical Research

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