Disease relevance of Genes, sis

• The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule [1].
• PDGF B is homologous to the v-sis oncogene of simian sarcoma virus (SSV), and certain deletions confined to 3; and 5; non-coding sequences of PDGF B mRNA are consistently found in tumors induced by SSV and by a PDGF B retrovirus [2].
• This may be exemplified by the human malignant glioma, in which the sis gene (encoding a growth factor homologous to PDGF) and the erb B gene (encoding a membrane protein homologous to the EGF receptor) have been implicated [3].
• Fusion of the collagen type I a 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been pointed out in dermatofibrosarcoma protuberans [4].

High impact information on Genes, sis

• The gene encoding PDGF-B has given rise to the v-sis oncogene [5].
• Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-sis oncogene [6].
• The v-sis oncogene encodes a platelet-derived growth factor (PDGF)-related product whose transforming activity is mediated by its functional interaction with the PDGF receptor [7].
• Site-directed mutagenesis of the v-sis gene revealed that each conserved cysteine residue was required directly or indirectly for disulfide-linked dimer formation [7].
• We have constructed a NIH3T3 cell line which contains the v-sis gene under the inducible control of the Drosophila melanogaster hsp70 promoter [8].

Biological context of Genes, sis

• Differences in the structure and processing of the v-sis gene product in procaryotic and eucaryotic cells provided important insights concerning posttranslational modifications of this PDGF-related transforming protein in eucaryotic cells [9].
• These cysteine residues were also important for dimerization of the v-sis gene product, since all of the nontransforming v-sis deletions were unable to form dimers when they were analyzed under nonreducing conditions [10].
• When the expression of the N-myc, c-myc, and sis oncogenes and tumorigenicity were examined in the same hybrid cells, no correlation was found, suggesting that the expression of these oncogenes in these hybrid cells did not appear to be controlled by putative "tumor suppressor" genes [11].
• Like the v-sis gene product, the PDGF-2 precursor undergoes N-linked glycosylation, implying its processing through the endoplasmic reticulum [12].
• These responses required transfection of a threshold level of repair cells, achievable only in injured muscles, and were transgene-driven, as neither platelet-derived growth factor-B (PDGFB) gene nor FGF2 protein delivery produced equivalent responses [13].

Anatomical context of Genes, sis

• Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells [14].
• CD44 protein levels and its biological activity are regulated in Balb/c 3T3 fibroblasts by serum factors and by transformation with the ras but not with the sis oncogene [15].
• CD44s (standard isoform) levels and hyaluronan-binding activity were investigated in Balb/c 3T3 cells and their derivatives transformed with ras or sis oncogenes as a function of serum concentration in the medium [15].
• In many tumor cell lines, including some transformed by the ras and sis oncogenes, activation of protein kinase A by elevation of cyclic AMP or activation of protein kinase C by addition of phorbol esters can restore many normal aspects of growth and morphology [16].
• The first component, which eluted at 0.8 M NaCl, is able to induce autophosphorylation of the platelet-derived growth factor (PDGF) receptor, is a mitogen for Swiss 3T3 cells and corresponds to the PDGF B chain product of the v-sis oncogene [17].

Associations of Genes, sis with chemical compounds

• The role of individual cysteine residues in the structure and function of the v-sis gene product [7].
• Removal of the N-linked glycosylation site from the v-sis gene product did not prevent cell surface transport [18].
• Oligonucleotide-directed mutagenesis was used to change the Cys codons to Ser codons in the v-sis gene [19].
• CRSBP-1, like the v-sis gene product and PDGF beta-type receptor, underwent rapid turnover which was blocked in the presence of 100 microM suramin [20].
• CRSBP-1 expressed in transfected cells is an approximately 120-kDa disulfide-linked homodimeric glycoprotein and exhibits dual ligand (CRS-containing growth regulators (v-sis gene product and insulin-like growth factor binding protein-3, IGFBP-3) and hyaluronic acid) binding activity [21].

Gene context of Genes, sis

• DFSP and GCF tumors are genetically characterized by chromosomal rearrangements fusing the collagen type Ialpha1 (COLIA1) gene to the platelet-derived growth factor B-chain (PDGFB) gene [22].
• The v-sis oncogene encodes a protein structurally and functionally related to human platelet-derived growth factor (PDGF) [12].
• All three SSV-transformed cells secreted v-sis gene product (p44). p44 was secreted but remained tightly associated with the cell surface [23].
• The results showed that when complemented either by a ras oncogene expressed at a somewhat enhanced level or by the v-sis oncogene, v-fes can supply the additional change required for malignant transformation [24].
• Because these responses play key roles in lung injury, PDGF-B (c-sis) gene expression was measured by Northern blot analysis of lung total RNA prepared after oxidant injury was induced by chronic exposure of rats to 85% oxygen for zero, 1, 3, and 7 days [25].

Analytical, diagnostic and therapeutic context of Genes, sis

• Southern blot experiments using probes specific for bcr and c-sis however revealed rearrangement of the bcr, but not of PDGFB (c-sis) gene [26].

References