RGD Reference Report - Increased expression of platelet-derived growth factor associated protein-1 is associated with PDGF-B mediated glioma progression. - Rat Genome Database

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Increased expression of platelet-derived growth factor associated protein-1 is associated with PDGF-B mediated glioma progression.

Authors: Sharma, Vinay Kumar  Singh, Anand  Srivastava, Sandeep Kumar  Kumar, Vignesh  Gardi, Nilesh Laxman  Nalwa, Aasma  Dinda, Amit Kumar  Chattopadhyay, Parthaprasad  Yadav, Savita 
Citation: Sharma VK, etal., Int J Biochem Cell Biol. 2016 Sep;78:194-205. doi: 10.1016/j.biocel.2016.07.016. Epub 2016 Jul 19.
RGD ID: 13702895
Pubmed: PMID:27448842   (View Abstract at PubMed)
DOI: DOI:10.1016/j.biocel.2016.07.016   (Journal Full-text)

The current treatment therapies available for malignant gliomas are inadequate. There is an urgent need to develop more effective therapies by characterizing the molecular pathogenesis of the disease. Over expression of platelet-derived growth factor (PDGF) ligands and receptors have been reported in malignant gliomas. Platelet-derived growth factor associated protein-1 (PDAP-1) is reported to modulate the mitogenic activity of PDGF ligands, but to date, there is no information concerning its role in PDGF-mediated glioma cell proliferation. This study aimed to characterize the role of PDAP-1 in PDGF-mediated glioma proliferation. The expression of PDAP-1 was observed to be significantly increased (p<0.05) in grade IV glioma tissue and cell lines compared to grade III. siRNA-mediated knockdown of PDAP-1 reduced the expression of PDGF-B and its downstream genes (Akt1/Protein kinase B (PKB) and phosphoinositide-dependent kinase-1 (PDK1) by up to 50%. In PDAP-1 knockdown glioma cells, more than a twofold reduction was also observed in the level of phosphorylated Akt. Interestingly, knockdown of PDAP-1 in combination with PDGF-B antibody inhibited glioma cell proliferation through activation of Caspase 3/7 and 9. We also demonstrate that PDAP-1 co-localizes with PDGF-B in the cytoplasm of glioma cells, and an interaction between both of the proteins was established. Collectively, these findings suggest that the expression of PDAP-1 is associated with disease malignancy, and its inhibition reduced the proliferation of malignant glioma cells through down-regulation of PDGF-B/Akt/PDK1 signaling. Thus, this study establishes PDAP-1 as an effecter of PDGF signaling in glioma cells and suggests that it could also be a promising therapeutic target.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDAP1Humanhigh grade glioma severityIEP  RGD 
PDGFBHumanhigh grade glioma severityIEP  RGD 
Pdap1Rathigh grade glioma severityISOPDAP1 (Homo sapiens) RGD 
Pdap1Mousehigh grade glioma severityISOPDAP1 (Homo sapiens) RGD 
PdgfbRathigh grade glioma severityISOPDGFB (Homo sapiens) RGD 
PdgfbMousehigh grade glioma severityISOPDGFB (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdap1  (PDGFA associated protein 1)
Pdgfb  (platelet derived growth factor subunit B)

Genes (Mus musculus)
Pdap1  (PDGFA associated protein 1)
Pdgfb  (platelet derived growth factor, B polypeptide)

Genes (Homo sapiens)
PDAP1  (PDGFA associated protein 1)
PDGFB  (platelet derived growth factor subunit B)


Additional Information