TY - JOUR AU - George, Sarah J. AB - Molecular Medicine Regulation of Smooth Muscle Cell Proliferation by -Catenin/T-Cell Factor Signaling Involves Modulation of Cyclin D1 and p21 Expression Helen Quasnichka, Sadie C. Slater, Cressida A. Beeching, Manfred Boehm, Graciela B. Sala-Newby, Sarah J. George Abstract—We previously observed that stimulation of vascular smooth muscle cell (VSMC) proliferation with growth factors is associated with dismantling of cadherin junctions and nuclear translocation of -catenin. In this study we demonstrate directly that growth factors stimulate -catenin/T-cell factor (TCF) signaling in primary VSMCs. To determine whether -catenin/TCF signaling regulates VSMC proliferation via modulation of the -catenin/TCF responsive cell cycle genes, cyclin D1 and p21, we inhibited -catenin/TCF signaling by adenoviral-mediated over-expression of N-Cadherin, ICAT (an endogenous inhibitor of -catenin/TCF signaling), or a dominant negative (dn) mutant of TCF-4. N-cadherin, ICAT or dnTCF-4 over-expression significantly reduced proliferation of isolated human VSMCs by approximately 55%, 80%, and 45% respectively. Similar effects were observed in human saphenous vein medial segments where proliferation was reduced by approximately 55%. Transfection of dnTCF-4 in the ISS10 human VSMC line significantly lowered TCF and cyclin D1 reporter activity but significantly elevated p21 reporter activity, indicating regulation of these genes by -catenin/TCF signaling. In support of this, over-expression of N-cadherin, TI - Regulation of Smooth Muscle Cell Proliferation by &bgr;-Catenin/T-Cell Factor Signaling Involves Modulation of Cyclin D1 and p21 Expression JF - Circulation Research DO - 10.1161/01.RES.0000253533.65446.33 DA - 2006-12-01 UR - https://www.deepdyve.com/lp/wolters-kluwer-health/regulation-of-smooth-muscle-cell-proliferation-by-bgr-catenin-t-cell-Q9SCLjM0B6 SP - 1329 EP - 1337 VL - 99 IS - 12 DP - DeepDyve ER -