Carcinogenesis and Neoplasia ... a Companion Site.


Human c-sis/PDGF-β proto-oncogene is overexpressed in a large percentage of human tumor cells involving a growth-promoting, autocrine growth circuit. The c-sis/PDGF-β promoter contains a unique homopurine/homopyrimidine sequence (SIS proximal element, SPE), which is crucial for transciption stimulating nuclear-binding factors.[1] The human sis gene is located at 22q12.3-13.1 on the long arm of chromosome 22.

: malignant pathology : non-malignant pathology : PDGF, platelet derived growth factor : v-sis :

The v-sis oncogene of the simian sarcoma virus is a retroviral homolog of the cellular gene encoding the β chain of PDGF (9,10) The hypothesis that unscheduled production of PDGF may contribute to the growth of spontaneous tumors is supported by the finding that PDGF is frequently produced by cell lines from human tumors such as glioblastoma and fibrosarcoma (11), melanoma (12), breast carcinoma (13), lung carcinoma (14), glioma (15), esophageal carcinoma (16) and Kaposi’s sarcoma (17). Gene transfer experiments have shown that overexpression of the normal human PDGF-β gene (c-sis, proto-oncogene) can cause the generation of fibrosarcoma (18), vascular connective tissue stroma with no necrosis (19) and tumorigenic and metastatic effects (2022). [3]

Regulation of expression of platelet derived growth factor polypeptide B encoded by the c-sis proto-oncogene is important in a number of physiological and pathological conditions.[2] Sequences upstream of the c-sis RNA CAP site respond to the HTLV-I transactivator protein to increase RNA synthesis from either the c-sis or HTLV I promoter. [2]

Platelet-derived growth factor (PDGF) is a ubiquitous, potent mitogen and chemotactic factor for many connective tissue cells. PDGF occurs as a three-disulfide-linked dimer composed of two homologous chains, α and β (1,2). The biological function of PDGF is mediated through binding to two cell surface proteins, PDGF receptors α and ß (35). Binding of PDGF to the extracellular part of either receptor type leads to dimerization of receptor molecules, followed by activation of the receptor protein-tyrosine kinase (6) and generation of phosphorylation-mediated signals that initiate the biological response (7,8).

PDGF has been implicated in the pathogenesis of several non-malignant proliferative diseases including atherosclerosis (2324), fibrosis (25), restenosis following vascular angioplasty (26), giant cell arteritis (27), aseptic loosening (28) and bronchiolitis obliterans syndrome (29). [3]

: malignant pathology : non-malignant pathology : PDGF, platelet derived growth factor : v-sis :
Tables  Oncogenes Proto-oncogenes  Malignant Transformation  Regulatory Proteins Sequences  Cell signaling  Cell Adhesion  Apoptosis vs Necrosis  Apoptosis 


Labels: , ,

. . . proliferating since 10/06/06