RGD Reference Report - Activation of PI3Kγ/Akt pathway mediates bone cancer pain in rats. - Rat Genome Database

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Activation of PI3Kγ/Akt pathway mediates bone cancer pain in rats.

Authors: Guan, Xuehai  Fu, Qiaochu  Xiong, Bingrui  Song, Zhenpeng  Shu, Bin  Bu, Huilian  Xu, Bing  Manyande, Anne  Cao, Fei  Tian, Yuke 
Citation: Guan X, etal., J Neurochem. 2015 Aug;134(3):590-600. doi: 10.1111/jnc.13139. Epub 2015 Jun 4.
RGD ID: 152025537
Pubmed: PMID:25919859   (View Abstract at PubMed)
DOI: DOI:10.1111/jnc.13139   (Journal Full-text)

Bone cancer pain (BCP) is one of the most common and severe complications in patients suffering from primary bone cancer or metastatic bone cancer such as breast, prostate, or lung, which profoundly compromises their quality of life. Emerging lines of evidence indicate that central sensitization is required for the development and maintenance of BCP. However, the underlying mechanisms are largely unknown. In this study, we investigated the role of PI3Kγ/Akt in the central sensitization in rats with tumor cell implantation in the tibia, a widely used model of BCP. Our results showed that PI3Kγ and its downstream target pAkt were up-regulated in a time-dependent manner and distributed predominately in the superficial layers of the spinal dorsal horn neurons, astrocytes and a minority of microglia, and were colocalized with non-peptidergic, calcitonin gene-related peptide-peptidergic, and A-type neurons in dorsal root ganglion ipsilateral to tumor cell inoculation in rats. Inhibition of spinal PI3Kγ suppressed BCP-associated behaviors and the up-regulation of pAkt in the spinal cord and dorsal root ganglion. This study suggests that PI3Kγ/Akt signal pathway mediates BCP in rats. Central sensitization is required for the development and maintenance of bone cancer pain (BCP). In this study, we reported that PI3Kγ/Akt mediated the function of ephrinBs/EphBs in the central sensitization under BCP condition, and inhibition of spinal PI3Kγ suppressed BCP-associated behaviors. Our results suggest that inhibition of PI3Kγ/Akt may be a new target for the treatment of BCP.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PIK3CGHumanCancer Pain  ISOPik3cg (Rattus norvegicus)mRNA and protein:increased expression:spinal cord (rat)RGD 
Pik3cgRatCancer Pain  IEP mRNA and protein:increased expression:spinal cord (rat)RGD 
Pik3cgMouseCancer Pain  ISOPik3cg (Rattus norvegicus)mRNA and protein:increased expression:spinal cord (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pik3cgRatbehavioral response to pain treatmentIDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma)

Genes (Mus musculus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)

Genes (Homo sapiens)
PIK3CG  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)


Additional Information