Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes.

Background: The adipose tissue is important for development of insulin resistance and type 2 diabetes and adipose tissue dysfunction has been proposed as an underlying cause. In the present study we investigated presence of adipocyte hypertrophy, and gene expression pattern of adipose tissue dysfunction in the subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes compared to matched control subjects with no known genetic predisposition for type 2 diabetes.

Method: Seventeen healthy and non-obese subjects with known genetic predisposition for type 2 diabetes (first-degree relatives, FDRs) and 17 control subjects were recruited.

Characterization of integrin and anchorage dependence in mammary epithelial cells following c-erbB2-induced epithelial-mesenchymal transition.

Signalling from the proto-oncogene c-erbB2 in mammary epithelial cells has earlier been shown to result in epithelial-mesenchymal transition (EMT) giving rise to fibroblast-like cells, and acquisition of anchorage-independent growth (AIG) usually determined by growth capacity in soft agar. In this study, we have analysed AIG associated with c-erbB2-induced EMT in a human mammary epithelial cell line. Intriguingly, cells capable of growth in soft agar were shown to be dependent on the function of beta(1) integrin extracellular matrix receptors for growth in collagen.

c-erbB2-induced epithelial-mesenchymal transition in mammary epithelial cells is suppressed by cell-cell contact and initiated prior to E-cadherin downregulation.

Prolonged signalling from the growth factor receptor subunit and proto-oncogene c-erbB2 has been shown to cause epithelial-mesenchymal transition (EMT) in mammary epithelial cells. Using a system where c-erbB2 homodimer signalling can be induced in human mammary epithelial cells, we characterised the properties of c-erbB2-induced EMT. The cells resulting from this transdifferentiation showed a pronounced and stable fibroblastic phenotype with spindle-like morphology, homogeneous high expression of vimentin, N-cadherin, and integrin alpha5 as well as loss of E-cadherin and desmoplakin.

PKB mediates c-erbB2-induced epithelial beta1 integrin conformational inactivation through Rho-independent F-actin rearrangements.

Signalling from the growth factor receptor subunit and proto-oncogene c-erbB2 has been shown to inhibit the adhesive function of the collagen receptor integrin alpha(2)beta(1) in human mammary epithelial cells. This anti-adhesive effect is mediated by the MAP ERK kinase 1/2 (MEK1/2) and protein kinase B (PKB) pathways. Here, we show that both pathways mediate suppression of matrix adhesion by causing the extracellular domain of the beta(1) integrin subunit to adopt an inactive conformation.