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2011 | 14 | 1 |
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Gene expression pattern in canine mammary osteosarcoma

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Canine mammary sarcomas are usually very aggressive and easily metastasize. Unfortunately the biology of this type of tumor is not well known because they are a very rare type of tumors. The aim of this study was to find differences in gene expression patterns in canine mammary osteosarcomas (malignant) versus osteomas (benign) using DNA microarrays. Our microarray experiment showed that 11 genes were up-regulated in osteosarcoma in comparison to osteoma whereas 36 genes were down-regulated. Among the up-regulated genes were: PDK1, EXT1, and EIF4H which are involved in AKT/PI3K and GLI/Hedgehog pathways. These genes play an important role in cell biology (cancer cell proliferation) and may be essential in osteosarcoma formation and development. Analyzing the down-regulated genes, the most interesting seemed to be HSPB8 and SEPP1. HSPB8 is a small heat shock protein that plays an important role in cell cycle regulation, apoptosis, and breast carcinogenesis. Also SEPP1 may play a role in carcinogenesis, as its down-regulation may induce oxidative stress possibly resulting in carcinogenesis. The preliminary results of the present study indicate that the up-regulation of three genes EXT1, EIF4H, and PDK1 may play an essential role in osteosarcoma formation, development and proliferation. In our opinion the cross-talk between GLI/Hedgehog and PI3K/AKT pathways may be a key factor to increase tumor proliferation and malignancy.
Opis fizyczny
  • Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences – WULS, Nowoursynowska 159, 02-776 Warsaw, Poland
  • Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P (1997) Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B[alpha]. Curr Biol 7: 261-269.
  • Alessi DR, Kozlowski MT, Weng QP, Morrice N, Avruch J (1998) 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Curr Biol 8: 69-81.
  • Balendran A, Hare GR, Kieloch A, Williams MR, Alessi DR (2000) Further evidence that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is required for the stability and phosphorylation of protein kinase C (PKC) isoforms. FEBS Lett 484: 217-223.
  • Bordeleau ME, Cencic R, Lindqvist L, Oberer M, Northcote P, Wagner G, Pelletie J (2006) RNA-mediated sequestration of the RNA helicase eIF4A by pateamine A inhibits translation initiation. Chem Biol 13: 1287-1295.
  • Brinkhof B, Spee B, Rothuizen J, Penning LC (2006) Development and evaluation of canine reference genes for accurate quantification of gene expression. Anal Biochem 356: 36-43.
  • Cen L, Hsieh FC, Lin HJ, Chen CS, Qualman SJ, Lin J (2007) PDK-1/AKT pathway as a novel therapeutic target in rhabdomyosarcoma cells using OSU-03012 compound. Br J Cancer 97: 785-791.
  • Clark AS, West K, Streicher S, Dennis PA (2002) Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 1: 707-717.
  • Cooper ML, Adami HO, Gronberg H, Wiklund F, Green FR, Rayman MP (2008) Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk. Cancer Res 68: 10171-10177.
  • Etschmann B, Wilcken, B, Stoevesand K, von der Schulenburg A, Sterner-Kock A (2006) Selection of reference genes for quantitative real-time PCR analysis in canine mammary tumors using the GeNorm algorithm. Vet Pathol 43: 934-942.
  • Gartner F, Geraldes M, Cassali G, Rema A, Schmitt F (1999) DNA measurement and immunohistochemical characterization of epithelial and mesenchymal cells in canine mixed mammary tumours: putative evidence for a common histogenesis. Vet J 158: 39-47.
  • Gresner P, Gromadzinska J, Jablonska E, Kaczmarski J, Wasowicz W (2009) Expression of selenoprotein-coding genes SEPP1, SEP15 and hGPX1 in non-small cell lung cancer. Lung Cancer 65: 34-40.
  • Hellmen E, Bergstrom R, Holmberg L, Spangberg IB, Hansson K, Lindgren A (1993) Prognostic factors in canine mammary tumors: a multivariate study of 202 consecutive cases. Vet Pathol 30: 20-27.
  • Hellmen E, Moller M, Blankenstein MA, Andersson L, Westermark B (2000) Expression of different phenotypes in cell lines from canine mammary spindle-cell tumours and osteosarcomas indicating a pluripotent mammary stem cell origin. Breast Cancer Res Treat 61: 197-210.
  • Król M, Pawłowski KM, Skierski J, Rao NA, Hellmen E, Mol JA, Motyl T (2009) Transcriptomic profile of two canine mammary cancer cell lines with different proliferative and anti-apoptotic potential. J Physiol Pharmacol 60: 95-106.
  • Król M, Polańska J, Pawłowski KM, Turowski P, Skierski J, Majewska A, Ugorski M, Morty RE, Motyl T (2010a) Transcriptomic signature of cell lines isolated from canine mammary adenocarcinoma metastases to lungs. J Appl Genet 51: 37-50.
  • Król M, Pawłowski KM, Skierski J, Turowski P, Majewska A, Polańska J, Ugorski M, Morty RE, Motyl T (2010b) Transcriptomic “portraits” of canine mammary cancer cell lines with various phenotypes. J Appl Genet 51: 169-183.
  • Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P, Parker PJ (1998) Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science 281: 2042-2045.
  • Leibl S, Moinfar F (2006) Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of myoepithelial differentiation. Am J Surg Pathol 30: 450-456.
  • Levine RE, Forest T, Smith C (2002) Tumor suppressor PTEN is mutated in canine osteosarcoma cell lines and tumors. Vet Pathol 39: 372-378.
  • Mamane Y, Petroulakis E, Rong L, Yoshida K, Ler LW, Sonenberg N (2004) eIF4E – from translation to transformation. Oncogene 23: 3172-3179.
  • Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, Wu J, Nandula S, Dutta B, Xie Y, Chin YR, Kim DI, Ferris JS, Gruvberger-Saal SK, Laakso M, Wang X, Memeo L, Rojtman A, Matos T, Yu JS, Cordon-Cardo C, Isola J, Terry MB, Toker A, Mills GB, Zhao JJ, Murty VV, Hibshoosh H, Parsons R (2009) 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Cancer Res 69: 6299-6306.
  • Mi H, Lazareva-Ulitsky B, Loo R, Kejariwal A, Vandergriff J, Rabkin S, Guo N, Muruganujan A, Doremieux O, Campbell MJ, Kitano H, Thomas PD (2005) The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic Acids Res 33: D284-288. de los Monteros AE, Millan MY, Ramirez GA, Ordas J, Reymundo C, de las Mulas JM (2005) Expression of maspin in mammary gland tumors of the dog. Vet Pathol 42: 250-257.
  • Mora A, Komander D, van Aalten DM, Alessi DR (2004) PDK1, the master regulator of AGC kinase signal transduction. Semin Cell Dev Biol 15: 161-170.
  • Nesterov A, Lu X, Johnson M, Miller GJ, Ivanshchenko Y, Kraft AS (2001) Elevated AKT activity protects the prostate cancer cell line LNCaP from TRAIL-induced apoptosis. J Biol Chem 276: 10767-10774.
  • Page C, Lin HJ, Jin Y, Castle VP, Nunez G, Huang M, Lin J (2000) Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis. Anticancer Res 20: 407-416.
  • Pawłowski KM, Król M, Majewska A, Badowska-Kozakiewicz A, Mol JA, Malicka E, Motyl T (2009) Comparison of cellular and tissue transcriptional profiles in canine mammary tumor. J Physiol Pharmacol 60: 85-94.
  • Pilar S, Clement V, Ruiz i Altaba A (2005) Therapeutic targeting of the Hedgehog-GLI pathway in prostate cancer. Cancer Res 65: 2990-2992.
  • Polyak K (2007) Breast cancer: origins and evolution. J Clin Invest 117: 3155-3163.
  • Rao NA, van Wolferen ME, van den Ham R, van Leenen D, Groot Koerkamp MJ, Holstege FC, Mol JA (2008) cDNA microarray profiles of canine mammary tumor cell lines reveal deregulated pathways pertaining to their phenotype. Anim Genet 39: 333-345.
  • Rao NA, van Wolferen ME, Gracanin A, Bhatti SF, Król M, Holstege FC, Mol JA (2009) Gene expression profiles of progestin-induced canine mammary hyperplasia and spontaneous mammary tumors. J Physiol Pharmacol 60: 73-84.
  • Rogers GW Jr, Richter NJ, Lima WF, Merrick WC (2001) Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F. J Biol Chem 276: 30914-30922.
  • Sobczak-Filipiak M, Malicka E (2002) Estrogen receptors in canine mammary gland tumours. Pol J Vet Sci 5: 1-5.
  • Stecca B, Mas C, Clement V, Zbinden M, Correa R, Piguet V, Beermann F, Ruiz I Altaba A (2007) Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci USA 104: 5895-5900.
  • Stecca B, Ruiz I Altaba A (2010) Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J Mol Cell Biol 2: 84-95.
  • Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, McCormick F, Hawkins PT (1997) Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277: 567-570.
  • Trent S, Yang C, Li C, Lynch M, Schmidt EV (2007) Heat shock protein B8, a cyclin-dependent kinase-independent cyclin D1 target gene, contributes to its effects on radiation sensitivity. Cancer Res 67: 10774-10781.
  • Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10: 789-799.
  • Wensman H, Goransson H, Leuchowius KJ, Stromberg S, Ponten F, Isaksson A, Rutteman GR, Heldin NE, Pejler G, Hellmen E (2009) Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas. Breast Cancer Res Treat 118: 333-343.
  • Xie Z, Zeng X, Waldman T, Glazer RI (2003) Transformation of mammary epithelial cells by 3-phosphoinositidedependent protein kinase-1 activates beta-catenin and c-Myc, and down-regulates caveolin-1. Cancer Res 63: 5370-5375.
  • Xie Z, Yuan H, Yin Y, Zeng X, Bai R, Glazer RI (2006) 3-phosphoinositide-dependent protein kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases. BMC Cancer 6: 77.
  • Zeng X, Xu H, Glazer RI (2002) Transformation of mammary epithelial cells by 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with the induction of protein kinase C alpha. Cancer Res 62: 3538-3543.
  • Zeynep ME, Kieser KJ, Kim SH, Komm B, Katzenellenbogen JS, Katzenellenbogen BS (2008) Nuclear and extranuclear pathway inputs in the regulation of global gene expression by estrogen receptors. Mol Endocrinol 22: 2116-2127.
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