Biopolym. Cell. 2003; 19(1):64-70.
Genome and Its Regulation
P70S6 kinase α and β isoforms expression in cell lines and breast tumors
1Savinskaya L. A., 2Usenko V. S., 2Lyzogubov V. V., 3Pogrebnoy P. V., 1Pal'chevsky S. S., 1Ovcharenko G. V., 4Cheshuk V. S., 1, 5Gout I. T., 1Matsuka G. Kh., 1Filonenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Pathomorphological Laboratory "BIONTEK"
    52A/88, Komsomol'ska Str., Dnipropetrovs'k, Ukraine, 49000
  3. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022
  4. Bogomolets National Medical University
    Blvd. Shevchenko, 13, Kyiv, Ukraine, 01601
  5. Ludwig Institute for Cancer Research
    91 Riding house str., London, UK, WIP8BT


P70 kinase of S6 ribosomal protein represented by α and β isoforms is among the key enzymes participating in the protein synthesis activation mediated by mitogenic signals. The expression of two p70S6 kinase isoforms in several cell lines as well as in malignant and non-malignant breast tumors was analyzed. The expression of both p70S6 kinase forms increased in all breast tumor cell lines examined. The enhanced synthesis of α and β isoforms in malignant tumors may reflect their important role in cancerogenesis. The increased levels of S6Kα expression comparable in malignant and non-malignant tumors have been shown for the first time.


[1] Valovka TI, Fiionenko VV, Palchevsky SS, Velikiy MM, Drobot LB, Waterfield M, Matsuka GKh, Gout IT. Functional and regulatory properties of p70S6 kinase b. Biopolym Cell 1999 15, N 5:415–421.
[2] Kozma SC, Ferrari S, Bassand P, Siegmann M, Totty N, Thomas G. Cloning of the mitogen-activated S6 kinase from rat liver reveals an enzyme of the second messenger subfamily. Proc Natl Acad Sci U S A. 1990;87(19):7365-9.
[3] Brown EJ, Schreiber SL. A signaling pathway to translational control. Cell. 1996;86(4):517-20.
[4] Gout I, Minami T, Hara K, Tsujishita Y, Filonenko V, Waterfield MD, Yonezawa K. Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region. J Biol Chem. 1998;273(46):30061-4.
[5] Lee-Fruman KK, Kuo CJ, Lippincott J, Terada N, Blenis J. Characterization of S6K2, a novel kinase homologous to S6K1. Oncogene. 1999;18(36):5108-14.
[6] Jeffenes HB, Thomas G. Ribosomal protein S6 phosphorylation and signal transduction. Translational control. Eds J . W. B. Hershey, M. B. Mathews, N. Sonenberg. New York: Cold Spring Harbor Lab. press, 1996: 389-409.
[7] Jefferies HB, Reinhard C, Kozma SC, Thomas G. Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family. Proc Natl Acad Sci U S A. 1994;91(10):4441-5.
[8] Lane HA, Fernandez A, Lamb NJ, Thomas G. p70s6k function is essential for G1 progression. Nature. 1993;363(6425):170-2.
[9] Kozma SC, Ferrari S, Thomas G. Unmasking a growth factor/oncogene-activated S6 phosphorylation cascade. Cell Signal. 1989;1(3):219-25.
[10] Simm A, Hoppe V, Karbach D, Leicht M, Fenn A, Hoppe J. Late signals from the PDGF receptors leading to the activation of the p70S6-kinase are necessary for the transition from G1 to S phase in AKR-2B cells. Exp Cell Res. 1998;244(2):379-93.
[11] Brennan P, Babbage JW, Thomas G, Cantrell D. p70(s6k) integrates phosphatidylinositol 3-kinase and rapamycin-regulated signals for E2F regulation in T lymphocytes. Mol Cell Biol. 1999;19(7):4729-38.
[12] Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma SC. Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J. 1998;17(22):6649-59.
[13] Kawasome H, Papst P, Webb S, Keller GM, Johnson GL, Gelfand EW, Terada N. Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity. Proc Natl Acad Sci U S A. 1998;95(9):5033-8.
[14] Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand-Brustel Y, Klumperman J, Thorens B, Thomas G. Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature. 2000 Dec 21-28;408(6815):994-7.
[15] Berven LA, Frew IJ, Crouch MF. Nitric oxide donors selectively potentiate thrombin-stimulated p70(S6k) activity and morphological changes in Swiss 3T3 cells. Biochem Biophys Res Commun. 1999;266(2):352-60.
[16] Berven LA, Crouch MF. Cellular function of p70S6K: a role in regulating cell motility. Immunol Cell Biol. 2000;78(4):447-51.
[17] Crouch MF. Regulation of thrombin-induced stress fibre formation in Swiss 3T3 cells by the 70-kDa S6 kinase. Biochem Biophys Res Commun. 1997;233(1):193-9.
[18] Harada H, Andersen JS, Mann M, Terada N, Korsmeyer SJ. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci U S A. 2001;98(17):9666-70.
[19] Couch FJ, Wang XY, Wu GJ, Qian J, Jenkins RB, James CD. Localization of PS6K to chromosomal region 17q23 and determination of its amplification in breast cancer. Cancer Res. 1999;59(7):1408-11.
[20] Wu GJ, Sinclair CS, Paape J, Ingle JN, Roche PC, James CD, Couch FJ. 17q23 amplifications in breast cancer involve the PAT1, RAD51C, PS6K, and SIGma1B genes. Cancer Res. 2000;60(19):5371-5.
[21] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
[22] Ausubel LJ, Krieger JI, Hafler DA. Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99. J Immunol. 1997;159(5):2502-12.
[23] Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227(5259):680-5.
[24] Savinska LO, Kijamova RG, Pogrebnoy PV, Ovtsharenko GV, Gout IT, Filonenko VV. Comparative characterization of S6 kinase ? and ? isoforms expression in mammalian tissues. Biopolym Cell. 2001; 17(5):374-9.
[25] Pogrebnoy PV, Kukharenko AP, Tykhonkova IA, Pal'chevskiy SS, Savinskaya LA, Pogrebnaya AP, Valevka TI, Markeeva NV, Soldatkina MA, Matsuka GKh, Gout IT, Filonenko VV. Generation and characterization of monoclonal antibodies to p70S6kinase. Exp Oncol. 1999; 21(4):232–8.
[26] Salh B, Marotta A, Wagey R, Sayed M, Pelech S. Dysregulation of phosphatidylinositol 3-kinase and downstream effectors in human breast cancer. Int J Cancer. 2002;98(1):148-54.