title: Effect of PI3K/Akt Signaling Pathway on the Process of Prostate Cancer Metastasis to Bone.
abstract: We sought to study the effects of PI3K/Akt pathway and its downstream substrate NF-κB on prostate cancer bone metastatic process. Expression level of active p-Akt in PC3 cells was upregulated by transient expression with constitutively active plasmid CA-Akt or, alternatively, suppressed by dominant negative construct DN-Akt. NF-κB activity was determined by luciferase reporter assays. mRNA and protein expressions of receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and bone morphogenetic protein 2 (BMP-2) were evaluated using RT-PCR and Western blotting. The effect of cross-talk between PC3 and SaOS2 cells on cell proliferation was analyzed using a co-culture system. Stimulation of p-Akt promoted NF-κB activity, and led to an increase in mRNA and protein expressions of RANKL, PTHrP, and BMP-2 in PC3 PCa cells through NF-κB. Co-culturing PC3 and SaOS2 cells significantly increased the expression of p-Akt and the activity of NF-κB, and promoted proliferation of both PC3 and SaOS2 cells. Increasing expression levels of p-Akt by transfection with CA-Akt led to further increase in cells proliferation, whereas NF-κB inhibitor PDTC partially blocked this effect. PI3K/Akt pathway stimulates the expressions of RANKL, PTHrP, and BMP-2 partly through NF-κB, suggesting its importance for bone metastasis of prostate carcinoma. Interaction of prostate cancer cells with bone cells has a stimulatory effect on cell proliferation.
authors.affiliation: Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
authors.forename: Jiguo
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. dryupeng@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Bone metastasis; NF-κB; PI3K/Akt; Prostate carcinoma