title: G Protein Alpha S Subunit Promotes Cell Proliferation of Renal Cell Carcinoma with Involvement of Protein Kinase A Signaling.
abstract: Heterotrimeric G proteins, which are composed of Gα and Gβγ subunits, transduce signals sensed by the coupled surface receptors. Aberrant expressions of G proteins have been observed in many cancer types. This study aimed to determine the expression level of the stimulatory G protein alpha S subunit (Gαs, the main transcript encoded by the GNAS locus) and its biological function in renal cell carcinoma (RCC). Western blotting and quantitative reverse transcription-PCR results show that Gαs expression dramatically increased in RCC cell lines (ACHN, GRC-1, and 786-O) compared to normal renal epithelial cells HK-2. Knockdown of Gαs by small interfering RNA (siRNA) caused a significant inhibition on proliferation of ACHN cells as indicated by MTT assay and colony formation assay. Overexpression of Gαs in HK-2 cells promoted cell proliferation and led to a higher level of intracellular cyclic adenosine monophosphate (cAMP) in response to parathyroid hormone (PTH) compared to the cells transfected with empty vector. Notably, the growth of HK-2 cells overexpressing Gαs was efficiently inhibited in the presence of protein kinase A (PKA) inhibitor H89. Furthermore, in a xenograft model by subcutaneous injection of ACHN cells, tumor growth was also suppressed by H89. Taken together, these results suggest that Gαs plays a tumor-promoting role in RCC and possibly acts through a PKA-dependent pathway. Our findings may provide new clues for target therapy for RCC in the future.
authors.affiliation: 1 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, People's Republic of China .
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 2 Tianjin Medical University , Tianjin, People's Republic of China .
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.affiliation: 3 Tianjin Central Hospital of Gynecology Obstetrics , Tianjin, People's Republic of China .
authors.forename: Xin
authors.initials: X
authors.lastname: Mu
authors.affiliation: 4 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry, Tianjin Medical University , Tianjin, People's Republic of China .
authors.forename: Lei
authors.initials: L
authors.lastname: Zhi
authors.affiliation: 5 Department of Orthopedic Surgery, The Affiliated Hospital of Logistics College of Chinese People's Armed Police Force , Tianjin, People's Republic of China .
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.affiliation: 1 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, People's Republic of China .
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 1 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, People's Republic of China .
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: 1 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, People's Republic of China .
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000072283:A549 Cells; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D007546:Isoquinolines; D010281:Parathyroid Hormone; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: G protein alpha S subunit; PKA; renal cell carcinoma