title: C5a stimulates the proliferation of breast cancer cells via Akt-dependent RGC-32 gene activation.
abstract: Complement system activation contributes to various immune and inflammatory diseases, as well as cancers.However, the role of complement activation in the proliferation of cancer cells is not clear. In the present study, we investigated the consequences of complement activation on the proliferation of breast cancer cells and its possible mechanisms. We focused our study on the potential roles of the anaphylatoxins C3a and C5a in the proliferation of human breast cancer, as two important immune mediators generated after complement activation. Our study revealed that C5a stimulation, but not C3a, enhanced the proliferation of human breast cancer cells in vitro. Moreover, the expression of response gene to complement 32 (RGC-32) was pronounced in breast cancer cells in response to C5a stimulation. Notably, blockade of the C5a receptor markedly reduced the expression of RGC-32 and the proliferation of breast cancer cells stimulated by C5a. Meanwhile, silencing of RGC-32 expression reduced the proliferation of breast cancer cells induced by C5a treatment. Further investigation revealed that Akt activation was involved in C5a-induced RGC-32 expression and breast cancer cell proliferation. In conclusion, the present study indicates that C5a may promote the proliferation of breast cancer cells through Akt1 activation of the RGC-32 gene.
authors.affiliation: Department of General Surgery, Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Suzhou, Jiangsu 215021, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Hu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D003176:Complement C3 / Q000235:genetics; D015936:Complement C5a / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C038245:C3 protein, human; C488033:C5AR1 protein, human; D018797:Cell Cycle Proteins; D003176:Complement C3; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt