The combined effects of tamoxifen, a competitive inhibitor of estrogen, and type I or II interferons on the proliferation of several human breast cancer cell lines in vitro were examined. Additive antiproliferative effects were observed with interferons and tamoxifen, in two estrogen receptor positive cell lines, MCF-7 and T-47D. In MCF-7 cells neither beta ser interferon, gamma interferon, nor...

background: the metabolically active tumor cells may be characterized by a pronounced adenosine release that regulates the growth and development of the tumor. consequently, the expression pattern of defined receptor subtypes will be an important determinant for specific effects of adenosine on the control of tumor cell growth. in recent studies, the expression profile, signal transduction, mol...

OBJECTIVE Phogrin and IA-2, autoantigens in insulin-dependent diabetes, have been shown to be involved in insulin secretion in pancreatic beta-cells; however, implications at a molecular level are confusing from experiment to experiment. We analyzed biological functions of phogrin in beta-cells by an RNA interference technique. RESEARCH DESIGN AND METHODS Adenovirus-mediated expression of sho...

FKBP12, the 12-kDa FK506-binding protein, is a ubiquitous abundant protein that acts as a receptor for the immunosuppressant drug FK506, binds tightly to intracellular calcium release channels and to the transforming growth factor beta (TGF-beta) type I receptor. We now demonstrate that cells from FKBP12-deficient (FKBP12(-/-)) mice manifest cell cycle arrest in G(1) phase and that these cells ...

The T-cell antigen receptor alpha-chain genes of an alloreactive, H-2Db-specific cytotoxic T-cell clone (3F9) are described. This study and our work on the 3F9 beta-chain genes reveal that the variable region gene segments for the alpha and beta chains expressed in 3F9 are identical to the ones used by a chicken erythrocyte-specific, I-Ab-restricted helper T-cell clone (LB2). These two clones d...

We compared integrin-mediated adhesion to extracellular matrix (ECM) components of cultured human melanocytes and 6 human melanoma cell lines with different metastatic capacities in nude mice. Cultured melanocytes and most melanoma cell lines adhered strongly to fibronectin (FN), whereas only highly metastatic cell lines adhered to laminin (LM), collagen type I (COI) and type IV (COIV). Adhesio...

The activity of the T-cell receptor beta-chain gene enhancer is increased by activators of the protein kinase C pathway during T-cell activation. Analysis of mutant enhancer constructs identified two elements, beta E2 and beta E3, conferring phorbol ester inducibility. Multimerized beta E2 acted in isolation as a phorbol ester-responsive element. Both beta E2 and beta E3, which contain a consen...

Despite treatment with agents that enhance beta-cell function and insulin action, reduction in beta-cell mass is relentless in patients with insulin resistance and type 2 diabetes mellitus. Insulin resistance is characterized by impaired signaling through the insulin/insulin receptor/insulin receptor substrate/PI-3K/Akt pathway, leading to elevation of negatively regulated substrates such as gl...

Regulating TGF-beta receptor presentation provides an avenue to alter a cell's responsiveness to TGF-beta. We report that activation of the Erk MAP kinase pathway decreases the TGF-beta-induced Smad3 activation due to decreased cell surface levels of the type I receptor TbetaRI, but not the type II receptor. Inhibition of TACE activity or expression enhanced the cell surface TbetaRI levels and ...