Disease relevance of TM7SF2

• These results, together with the reported fact that malignant gliomas express high levels of Ang1, suggest the existence of an autocrine loop in malignant gliomas and that a Tie2-dependent pathway modulates cell-to-extracellular matrix adhesion, providing new insights into the highly infiltrative phenotype of human gliomas [1].

High impact information on TM7SF2

• Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay [2].
• We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation [2].
• This effect of Ang1 could be prevented by wortmannin and LY-294002 pretreatment [3].
• TM7SF2 mRNA is most predominantly expressed in heart and DHCR7 mRNA mostly in liver and brain [4].
• The TM7SF2 gene contains 10 coding exons, and its intron positions are exactly conserved in the part of the LBR gene encoding its carboxyl-terminal domain [4].

Biological context of TM7SF2

• Sterol dependent regulation of human TM7SF2 gene expression: role of the encoded 3beta-hydroxysterol Delta14-reductase in human cholesterol biosynthesis [5].
• The transmembrane region of the putative TM7SF2 protein shows amino acid sequence similarity to those of the lamin B receptor and the C14/C24 sterol reductase [6].
• Identification and molecular characterization of TM7SF2 in the FAUNA gene cluster on human chromosome 11q13 [6].
• Angiopoietins 1 and 2 (Ang1 and Ang2) are regulators of both angiogenesis and lymphangiogenesis through the Tek/Tie-2 receptor tyrosine kinase [7].
• Conversely, the down-regulation of Tie2 levels by small interference RNA or the addition of soluble Tie2 abrogated the Ang1-mediated effect on cell adhesion [1].

Anatomical context of TM7SF2

• Besides the endoplasmic reticulum 3beta-hydroxysterol Delta(14)-reductase (C14SR) encoded by TM7SF2 gene, the lamin B receptor (LBR) of the inner nuclear membrane possesses 3beta-hydroxysterol Delta(14)-reductase activity, based on its ability to complement C14SR-defective yeast strains [5].
• COS-7 cells expressing the protein exhibited Delta 14-SR activity about sevenfold higher than control cells [8].
• RESULT(S): Angiopoietin 1 (ANG-1) expression was similar in non-menorrhagic and menorrhagic endometrium [9].
• The response of endothelial cells to stimulation with either Ang1 or Ang2 is thought to be dependent upon the origin of the endothelial cells [7].

Associations of TM7SF2 with chemical compounds

• In contrast, the sterol C14 reduction step and ergosterol prototrophy were restored in LBR-producing erg24 transformants which lack endogenous sterol C14 reductase [10].
• To test the effects of C14 reductase inhibitors on LBR activity, we constructed EMY54, an ergosterol-requiring strain that is devoid of both sterol C8-C7 isomerase and sterol C14 reductase activities [10].
• The increase of flk-1 and flt-1 (VEGF receptors) and tie-2 (Ang1 receptor) induced by ang II was significantly suppressed by PD123319 [11].
• Immunoreactivity of VEGF and Ang1 in cortical tubules was increased by ang II and was attenuated by losartan or PD123319 [11].

Other interactions of TM7SF2

• Their genes have recently been assigned the symbols TM7SF2 and DHCR7 [4].
• The induction of TM7SF2 gene expression is turned-on by promoter activation in response to low cell sterol levels and is mediated by SREBP-2 [5].
• Genes encoding chimeras of Neurospora crassa erg-3 and human TM7SF2 proteins fail to complement Neurospora and yeast sterol C-14 reductase mutants [12].

Analytical, diagnostic and therapeutic context of TM7SF2

• We examined mRNA and protein expression of angiopoietin 1 (Ang1) and Ang2 by semiquantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, and Western blot in BAVMs and control brains obtained from temporal lobectomy for medically intractable seizures [13].

References