Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.

AdipoQ is a novel adipose-specific gene dysregulated in obesity.

https://www.cell.com/cell/pdf/S0092-8674(00)81575-5.pdf

PPARγ Promotes Monocyte/Macrophage Differentiation and Uptake of Oxidized LDL

Malignant cells are known to have accelerated metabolism, high glucose requirements, and increased glucose uptake. Transport of glucose across the plasma membrane of mammalian cells is the first rate-limiting step for glucose metabolism and is mediated by facilitative glucose transporter (GLUT) proteins. Increased glucose transport in malignant cells has been associated with increased and deregulated expression of glucose transporter proteins, with overexpression of GLUT1 and/or GLUT3 a characteristic feature. Oncogenic transformation of cultured mammalian cells causes a rapid increase of glucose transport and GLUT1 expression via interaction with GLUT1 promoter enhancer elements. In human studies, high levels of GLUT1 expression in tumors have been associated with poor survival. Studies indicate that glucose transport in breast cancer is not fully explained by GLUT1 or GLUT3 expression, suggesting involvement of another glucose transporter. Recently, a novel glucose transporter protein, GLUT12, has been found in breast and prostate cancers. In human breast and prostate tumors and cultured cells, GLUT12 is located intracellularly and at the cell surface. Trafficking of GLUT12 to the plasma membrane could therefore contribute to glucose uptake. Several factors have been implicated in the regulation of glucose transporter expression in breast cancer. Hypoxia can increase GLUT1 levels and glucose uptake. Estradiol and epidermal growth factor, both of which can play a role in breast cancer cell growth, increase glucose consumption. Estradiol and epidermal growth factor also increase GLUT12 protein levels in cultured breast cancer cells. Targeting GLUT12 could provide novel methods for detection and treatment of breast and prostate cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcp.20166

Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer

Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Muller cells. These data suggest that VEGF/VPF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization.

https://www.pnas.org/content/pnas/92/3/905.full.pdf

Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization

/pdf/36b4-cdna-used-as-an-estradiol-independent-mrna-control-is-2jhwt5yoj3.pdf

36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO

The effect of cholera toxin (CT) on the growth of 12 small cell lung carcinoma (SCLC) and 15 non-small cell lung carcinoma (NSCLC) cell lines is presented. CT inhibited the growth of nine SCLC cell lines (concentration for 50% inhibition of growth, 27–700 ng/ml), all of which had abundant expression of G M1 ganglioside, the surface receptor for CT. CT-resistant SCLC all had greatly decreased G M1 expression. In contrast, CT inhibited the growth of only four of 15 NSCLC cell lines. Seven of the 11 CT-resistant NSCLC had levels of G M1 comparable to CT-sensitive NSCLC or SCLC. In a limited panel of cell lines, cyclic AMP (cAMP) agonists including forskolin, 8Br[cAMP], and dibutyryl[cAMP] did not consistently reproduce CT-mediated inhibition of cell growth, nor did these compounds overcome resistance of cells to the growth inhibitory effects of CT. Expression of the R 1 and R I1 regulatory subunits of cAMP-dependent protein kinase was similar in CT-resistant and CT-sensitive SCLC or NSCLC cell lines. In the presence of isobutylmethylxanthine, intracellular cAMP levels induced by CT in a CT-resistant, G M1 (+) NSCLC cell line were comparable to those achieved in a CT-sensitive NSCLC cell line. We conclude that inhibition of lung carcinoma cell growth by CT in all cases requires expression of G M1 , and in the case of SCLC cell lines the presence of G M1 is sufficient. In NSCLC cell lines, expression of G M1 is not sufficient for growth inhibition by CT. These findings imply refractoriness to growth inhibition by cAMP in G M1 (+), CT-resistant NSCLC cell lines and the possibility of non-cAMP-related mechanisms for growth inhibition in CT-sensitive cell lines.

Jorge Laborda

Papers

36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO

Growth inhibition by cholera toxin of human lung carcinoma cell lines: correlation with GM1 ganglioside expression.