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Estrogenic effects are mediated through two estrogen receptor (ER) subtypes, ERα and ERβ. Estrogens are the most commonly prescribed drugs to treat menopausal conditions, but by non-selectively triggering both ERα and ERβ pathways in different tissues they can cause serious adverse effects. The different sizes of the binding pockets and sequences of their(More)
Expression of the Coxsackie and Adenovirus Receptor (CAR) is frequently reduced in carcinomas, resulting in decreased susceptibility of such tumors to infection with therapeutic adenoviruses. Because CAR participates physiologically in the formation of tight-junction protein complexes, we examined whether molecular mechanisms known to down-regulate(More)
The importance of perturbation in transforming growth factor beta (TGFbeta) signaling for the onset and progression of cancer is well established. Many tumors over express TGFbeta, and high circulating levels of TGFbeta1 in cancer patients are frequently associated with poor prognosis. TGFbeta has context-dependent biphasic action during tumorigenesis.(More)
TGF-β signalling has key functions in cell growth, differentiation, apoptosis, development and tumorigenesis. The mechanisms that lead to receptor activation and gene expression responses to TGF-β are generally understood 1. Binding of TGF-β to a complex of two type I and two type II kinase receptors, namely TβRI and TβRII, confers TβRI activation and(More)
Estrogen receptor beta (ERbeta) has potent antiproliferative and anti-inflammatory properties, suggesting that ERbeta-selective agonists might be a new class of therapeutic and chemopreventive agents. To understand how ERbeta regulates genes, we identified genes regulated by the unliganded and liganded forms of ERalpha and ERbeta in U2OS cells. Microarray(More)
Inhibition of PRL hormone signaling by suppressor of cytokine signaling (SOCS)/cytokine-inducible SH2-containing protein (CIS) was investigated in transfected HEK 293 cells. We used the physiologically relevant wild-type beta-casein promoter as a target gene for PRL action. We demonstrate that CIS produces a 70% inhibition of PRL signaling by a mechanism(More)
Post-translational sumoylation, the covalent attachment of a small ubiquitin-like modifier (SUMO), regulates the functions of proteins engaged in diverse processes. Often associated with nuclear and perinuclear proteins, such as transcription factors, it is not known whether SUMO can conjugate to cell-surface receptors for growth factors to regulate their(More)
3,3'-Diindolylmethane (DIM) is a natural compound found in cruciferous vegetables that has antiproliferative and estrogenic activity. However, it is not clear whether the estrogenic effects are mediated through estrogen receptor (ER)alpha, ERbeta, or both ER subtypes. We investigated whether DIM has ER subtype selectivity on gene transcription. DIM(More)
TGF-β is produced excessively by many solid tumors and can drive malignant progression through multiple effects on the tumor cell and microenvironment. TGF-β signaling pathway inhibitors have shown efficacy in preclinical models of metastatic cancer. Here, we investigated the effect of systemic LY2109761, a TGF-β type I/II receptor (TβRI/TβRII) kinase(More)
The F3-short form of the rat PRL receptor (F3-SPRLR) form acts as a dominant negative inhibitor in vitro. We have developed a transgenic mouse model in which the rat F3-SPRLR was expressed in mammary epithelium under the control of the mouse mammary tumor virus promoter. Two lines of mice were characterized and shown to express the transgene in the mammary(More)