Abstract
Vanadate and insulin both function as unique complete mitogens for SV40-transformed 3T3T cells, designated CSV3-1, but not for nontransformed 3T3T cells. The mitogenic effects induced by vanadate and insulin in CSV3-1 cells are mediated by different signaling mechanisms. For example, vanadate does not stimulate the tyrosine phosphorylation of the insulin receptor β-subunit nor the 170 kDa insulin receptor substrate-1. Instead, vanadate induces a marked increase in tyrosine phosphorylation of 55 and 64 kDa proteins that is not observed in insulin-stimulated CSV3-1 cells. Perhaps most interestingly, vanadate-induced mitogenesis is associated with the selective induction ofc-jun andjunB expression without significantly inducingc-fos orc-myc. Furthermore, treatment of CSV3-1 cells with genistein abolishes the effects of vanadate on protein tyrosine phosphorylation andc-jun induction. These and related data suggest that modulation of protein tyrosine phosphorylation andc-jun andjunB expression may serve the critical roles in mediating vanadate-induced mitogenesis in SV40-transformed cells.
Similar content being viewed by others
References
Shechter Y, Karlish SJD: Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558, 1980
Dubyak GR, Kleinzeller A: The insulin-mimetic effects of vanadate in isolated rat adipocytes: dissociation from effects of vanadate as a (Na+−K+)ATPase inhibitor. J Biol Chem 255: 5306–5312, 1980
Duckworth WC, Solomon SS, Liepnieks J, Hamel FG, Hand S, Peavy DE: Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinology 122: 2285–2289, 1988
Strout HV, Vicario PP, Biswas C, Saperstein R, Brady EJ, Pilch PF, Berger J: Vanadate treatment of streptozotocin diabetic rats restores expression of the insulin-responsive glucose transporter in skeletal muscle. Endocrinology 126: 2728–2732, 1990
Bollen M, Miralpeix M, Ventura F, Toth B, Bartrons R, Stalmans W: Oral administration of vanadate to streptozotocin-diabetic rats restores the glucose-induced activation of liver glycogen synthase. Biochem J 267: 269–271, 1990
Pugazhenthi S, Khandelwal RL: Insulinlike effects of vanadate on hepatic glycogen metabolism in nondiabetic and streptozocin-induced diabetic rats. Diabetes 39: 821–827, 1990
Shechter Y: Insulin-mimetic effects of vanadate: possible implication for future treatment of diabetes. Diabetes 39: 1–5, 1990
Shechter Y, Shisheva A: Vanadium salts and the future treatment of diabetes. Endeavour 17: 27–31, 1993
Heyliger CE, Tahiliani AG, McNeill JH: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227: 1474–1476, 1985
Valera A, Rodriguez-Gil JE, Bosch F: Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats. J Clin Invest 92: 4–11, 1993
Carpenter G: Vanadate, epidermal growth factor and the stimulation of DNA synthesis. Biochem Biophys Res Commun 102: 1115–1121, 1981
Smith JB: Vanadium ions stimulate DNA synthesis in Swiss mouse 3T3 and 3T6 cells. Proc Natl Acad Sci USA 80: 6162–6166, 1983
Ramanadham M, Kern M: Differential effect of vanadate on DNA synthesis induced by mitogens in T and B lymphocytes. Mol Cell Biochem 51: 67–71, 1983
Jones TR, Reid TW: Sodium orthovanadate stimulation of DNA synthesis in Nakano mouse lens epithelial cells in serum-free medium. J Cell Physiol 121: 199–205, 1984
Canalis E: Effects of sodium vanadate on deoxyribonucleic acid and protein syntheses in cultured rat calvariae. Endocrinology 116: 855–862, 1985
Lau KHW, Tanimoto H, Baylink DJ: Vanadate stimulates bone cell proliferation and bone collagen synthesisin vitro. Endocrinology 123: 2858–2867, 1988
Davidai G, Lee A, Schvartz I, Hazum E: PDGF induces tyrosine phosphorylation in osteoblast-like cells: relevance to mitogenesis. Am J Physiol 26: E205-E209, 1992
Maher PA: Stimulation of endothelial cell proliferation by vanadate is specific for microvascular endothelial cells. J Cell Physiol 151: 549–554, 1992
Raid A, Oliver B, Abdelrahman A, Sha'Afi RI, Hajjar J-J: Role of tyrosine kinase and phosphotyrosine phosphatase in growth of the intestinal crypt cell (IEC-6) line. Proc Soc Exp Biol Med 202: 435–439, 1993
Wang H, Wang J-Y, Johnson LR, Scott RE: Selective induction ofc-jun andjun-B but notc-fos orc-myc during mitogenesis in SV40-transformed cells at the predifferentiation growth arrest state. Cell Growth Differ 2: 645–652, 1991
Hori C, Oka T: Vanadate enhances the stimulatory action of insulin on DNA synthesis in cultured mouse mammary gland. Biochim Biophys Acta 610: 235–240, 1980
Montarras D, Pinset C, Dubois C, Chenevert J, Gros F: High level ofc-fos mRNA accumulation is not obligatory for renewed cell proliferation. Biochem Biophys Res Commun 153: 1090–1096, 1988
Sato B, Miyashita Y, Maeda Y, Noma K, Kishimoto S, Matsumoto K: Effects of estrogen and vanadate on the proliferation of newly established transformed mouse Leydig cell linein vitro. Endocrinology 120: 1112–1120, 1987
Kanakura Y, Druker B, Cannistra SA, Furukawa Y, Torimoto Y, Griffin JD: Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. Blood 76: 706–715, 1990
Klarlund JK: Transformation of cells by an inhibitor of phosphatases acting on phosphotyrosine in proteins. Cell 41: 707–717, 1985
Marchisio PC, D'Urso N, Comoglio PM, Giancotti FG, Tarone G: Vanadate-treated baby hamster kidney fibroblasts show cytoskeleton and adhesion patterns similar to their Rous sarcoma virus-transformed counterparts. J Cell Biochem 37: 151–159, 1988
Rijksen G, Voller MCW, Van Zoelen EJJ: Orthovanadate both mimics and antagonizes the transforming growth factor β action on normal rat kidney cells. J Cell Physiol 154: 393–401, 1993
Owada MK, Iwamoto M, Koike T, Kato Y: Effects of vanadate on tyrosine phosphorylation and the pattern of glycosaminoglycan synthesis in rabbit chondrocytes in culture. J Cell Physiol 138: 484–492, 1989
Dessureault J, Weber JM: Retransformation of a revertant cell line with the adenovirus E1 oncogenes and vanadate. J Cell Biochem 43: 293–296, 1990
Feldman RA, Lowy DR, Vass WC: Selective potentiation ofc-fps/fes transforming activity by a phosphatase inhibitor. Oncogene Res 5: 187–97, 1990
Kowalski LA, Tsang SS, Davison AJ: Vanadate enhances transformation of bovine papillomavirus DNA-transfected\({{C3H} \mathord{\left/ {\vphantom {{C3H} {10T{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}}}} \right. \kern-\nulldelimiterspace} {10T{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}}}\) cells. Cancer Lett 64: 83–90, 1992
Gordon JA: Use of vanadate as protein-phosphotyrosine phosphatase inhibitor. Methods Enzymol 201: 477–482, 1991
Kingsnorth AN, LaMuraglia GM, Ross JS, Malt RA: Vanadate supplements and 1,2-dimethylhydrazine induced colon cancer in mice: increased thymidine incorporation without enhanced carcinogenesis. Br J Cancer 53: 683–686, 1986
Fantus IG, Ahmad F, Deragon G: Vanadate augments insulin binding and prolongs insulin action in rat adipocytes. Endocrinology 127: 2716–2725, 1990
Fantus IG, Ahmad F, Deragon G: Vanadate augments insulin-stimulated insulin receptor kinase activity and prolongs insulin action in rat adipocytes: evidence for transduction of amplitude of signaling into duration of response. Diabetes 43: 375–383, 1994
Green A: The insulin-like effect of sodium vanadate on adipocyte glucose transport is mediated at a post-insulin-receptor level. Biochem J 238: 663–669, 1986
Strout HV, Vicario PP, Saperstein R, Slater EE: The insulin-mimetic effect of vanadate is not correlated with insulin receptor tyrosine kinase activity nor phosphorylation in mouse diaphragmin vivo. Endocrinology 124: 1918–1924, 1989
Wang H, Scott RE: Distinct protein tyrosine phosphorylation during mitogenesis induced in quiescent SV40-transformed 3T3 T cells by insulin or vanadate. J Cell Physiol 158: 408–416, 1994
D'Onofrio F, Le MQU, Chiasson J-L, Srivastava AK: Activation of mitogen activated protein (MAP) kinases by vanadate is independent of insulin receptor autophosphorylation. FEBS Lett 340: 269–275 1994
Nguyen TT, Scimeca J-C, Filloux C, Peraldi P, Carpentier J-L, Van Obberghen E: Co-regulation of the mitogen-activated protein kinase, extracellular signal-regulated kinase 1, and the 90-kDa ribosomal S6 kinase in the PC12 cells: distinct effects of the neurotrophic factors, nerve growth factor, and the mitogenic factor, epidermal growth factor. J Biol Chem 268: 9803–9810, 1993
White MF, Kahn CR: The insulin signaling system. J Biol Chem 269: 1–4, 1994
Pelech SL, Sanghera JS: Mitogen-activated protein kinases: versatile transducers for cell signaling. TIBS 17: 233–238, 1992
Swarup G, Cohen S, Garber DL: Inhibition of membrane phosphotyrosyl-protein phosphatase activity by vanadate. Biochem Biophys Res Commun 107: 1104–1109, 1982
Klarlund JK, Latini S, Forchhammer J: Numerous proteins phosphorylated on tyrosine and enhanced tyrosine kinase activities in vanadate-treated NIH 3T3 fibroblasts. Biochim Biophys Acta 971: 112–120, 1988
Shisheva A, Shechter Y: A cytosolic protein tyrosine kinase in rat adipocytes. FEBS Lett 300: 93–96, 1992
Shisheva A, Shechter Y: Role of cytosolic tyrosine kinase in mediating insulin-like actions of vanadate in rat adipocytes. J Biol Chem 268: 6463–6469, 1993
Elberg G, Li J, Shechter Y: Vanadium activates or inhibits receptor and non-receptor protein tyrosine kinases in cell-free experiments, depending on its oxidation state: possible role of endogenous vanadium in controlling cellular protein tyrosine kinase activity. J Biol Chem 269: 9521–9527, 1994
Cadena DL, Gill GN: Receptor tyrosine kinases. FASEB J 6: 2332–2337, 1992
Wang H, Scott RE: Insulin-induced mitogenesis associated with transformation by the SV40 large T antigen. J Cell Physiol 147: 102–110, 1991
Wang H, Scott RE: Induction ofc-jun independent of PKC, pertussis toxin-sensitive G protein, and polyamines in quiescent SV40-transformed 3T3 T cells. Exp Cell Res 203: 47–55, 1992
Filipak M, Estervig DN, Tzen CY, Minoo P, Hoerl BJ, Maercklein PB, Zschunke MA, Edens M, Scott RE: Integrated control of proliferation and differentiation of mesenchymal stem cells. Environ Health Perspect 80: 117–125, 1989
Wang H, Sturtevant DB, Scott RE: Nonterminal and terminal adipocyte differentiation of murine 3T3 T mesenchymal stem cells. In: J.E. Celis (ed.) Cell Biology: A Laboratory Handbook. Academic Press, San Diego 1994, pp 193–198
Hoerl BJ, Scott RE: Nonterminally differentiated cells express decreased growth factor responsiveness. J Cell Physiol 139: 68–75, 1989
Wang H, Scott RE: Inhibition of distinct steps in the adipocyte differentiation pathway in 3T3 T mesenchymal stem cells by dimethyl sulphoxide (DMSO). Cell Prolif 26: 55–66, 1993
Wang H, Scott RE: Adipocyte differentiation selectively represses the serum inducibility ofc-jun andjunB by reversible transcriptiondependent mechanisms. Proc Natl Acad Sci USA 91: 4649–4653, 1994
Estervig DN, Minoo P, Tzen CY, Scott RE: Inhibition of simian virus 40 T-antigen expression by cellular differentiation. J Virol 63: 2718–2725, 1989
Scott RE, Estervig DN, Tzen CY, Minoo P, Maercklein PB, Hoerl BJ: Nonterminal differentiation represses the neoplastic phenotype in spontaneously and simian virus 40-transformed cells. Proc Natl Acad Sci USA 86: 1652–1656, 1989
Estervig DN, Minoo P, Tzen CY, Scott RE: Three distinct effects of SV40 T-antigen gene transfection on cellular differentiation. J Cell Physiol 142: 552–558, 1990
Wang H, Scott RE: Autocrine inhibitor of terminal differenctation secreted by SV40-transformed 3T3 T cells. Mol Cell Differ 1: 345–355, 1993
Witte MM, Parker RF, Wang H, Scott RE: Repression of SV40 T oncoprotein expression by DMSO. J Cell Physiol 151: 50–55, 1992
Heffetz D, Bushkin I, Dror R, Zick Y: The insulinomimetic agents H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells. J Biol Chem 265: 2896–2902, 1990
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S-I, Itoh N, Shibuya M, Fukami Y: Genistein, a specific inhibitor of tyrosinespecific protein kinases. J Biol Chem 262: 5592–5595, 1987
Yin X, Davison AJ, Tsang SS: Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species. Mol Cell Biochem 115: 85–96, 1992
Davison AJ, Stern A, Fatur DJ, Tsang SS Vanadate stimulates ornithine decarboxylase activity in C3H/1oT1/2 cells. Biochem Int 24: 461–466, 1991
Itkes AV, Imamova LR, Alexandrova NM, Favorova OO, Kisselev LL: Expression ofc-myc gene in human ovary carcinoma cells treated with vanadate. Exp Cell Res 188: 169–71, 1990
Angel P, Karin M: The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072: 129–157, 1991
Kovary K, Bravo R: The Jun and Fos protein families are both required for cell cycle progression in fibroblasts. Mol Cell Biol 11: 4466–4472, 1991
Hughes M, Sehgal A, Hadman M, Bos T: Heterodimerization with c-Fos is not required for cell transformation of chicken embryo fibroblasts by Jun. Cell Growth Differ 3: 889–897, 1992
Suzuki T, Murakami M, Onai N, Fukuda E, Hashimoto Y, Sonobe MH, Kameda T, Ichinose M, Miki K, Iba H: Analysis of AP-1 function in cellular transformation pathways. J Virol 68: 3527–3535, 1994
Dong Z, Birrer MJ, Watts RG, Matrisian LM, Colburn NH: Blocking of tumor promoter induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells. Proc. Natl Acad Sci USA 91: 609–613, 1994
Kovary K, Bravo R: Existence of different Fos/Jun complexes during the G0-to-G1 trasition and during exponential growth in mouse fibroblasts: differential role of Fos proteins. Mol Cell Biol 12: 5015–5023, 1992
Angel P, Hattori K, Smeal T, Karin M: Thejun protooncogene is positively autoregulated by its product, Jun/AP-1. Cell 55: 875–885, 1988
Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR: Phosphorylation ofc-jun mediated by MAP kinases. Nature 353: 670–674, 1991
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wang, H., Scott, R.E. Unique and selective mitogenic effects of vanadate on SV40-transformed cells. Mol Cell Biochem 153, 59–67 (1995). https://doi.org/10.1007/BF01075919
Issue Date:
DOI: https://doi.org/10.1007/BF01075919