Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-20T01:22:33.665Z Has data issue: false hasContentIssue false
  • English
  • Français

Gene expression in Sinclair swine with malignant melanoma

Published online by Cambridge University Press:  22 September 2011

M. Okomo-Adhiambo ,
A. Rink ,
W. M. Rauw  and
L. Gomez-Raya
M. Okomo-Adhiambo
Affiliation:
Department of Animal Biotechnology, University of Nevada, 1664 North Virginia Street, 89557 Reno, NV, USA
A. Rink
Affiliation:
Department of Animal Biotechnology, University of Nevada, 1664 North Virginia Street, 89557 Reno, NV, USA Nevada Department of Agriculture, Animal Disease and Food Safety Laboratory, 350 Capitol Hill Avenue, 89502 Reno, NV, USA
W. M. Rauw
Affiliation:
Department of Animal Biotechnology, University of Nevada, 1664 North Virginia Street, 89557 Reno, NV, USA Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Carretera de La Coruña km 7.5, 28040 Madrid, Spain
L. Gomez-Raya*
Affiliation:
Department of Animal Biotechnology, University of Nevada, 1664 North Virginia Street, 89557 Reno, NV, USA Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Carretera de La Coruña km 7.5, 28040 Madrid, Spain
*
†E-mail: gomez.luis@inia.es
Get access

Abstract

Sinclair swine develop an aggressive form of melanoma, which, in many cases, spontaneously regresses after a complete metastatic phase. We used Affymetrix GeneChip® Porcine Genome Arrays consisting of 24 123 probe sets to compare gene expression in white blood cells (WBCs) and various tissues including the liver, lungs, inguinal lymph nodes and spleen harvested from a Sinclair piglet afflicted by melanoma at birth and exhibiting metastatic lesions at weaning (6 weeks) with those from a full-sibling piglet that showed no incidence of melanoma at birth and weaning. The highest number (3489; ∼14%) of significantly upregulated transcripts (fold change in gene expression ⩾2.0 and t-test P-value ≤0.05) was observed in the liver, while the spleen exhibited the lowest number of upregulated transcripts (528; ∼2%). Among significantly downregulated genes, the highest numbers were observed in the inguinal lymph nodes (3651; ∼15%) and the least in WBCs (730; ∼3%). Differentially expressed transcripts included genes involved in melanoma pathogenesis including SILV, TYR and RAB28. SILV was over-expressed 784-, 430- and 164-fold, while TYR was over-expressed 138-, 81- and 28-fold in the liver, lungs and inguinal lymph nodes, respectively. Quantitative real-time RT-PCR (qRT-PCR) confirmed the microarray data of 12 selected differentially expressed sequences. These results suggest that significant changes in gene expression occur during metastasis of malignant melanoma in the Sinclair swine model. In addition, qRT-PCR analysis of the above 12 differentially expressed sequences was carried out on liver samples collected from 22 pigs (12 of which had melanoma during the first 6 weeks of life), and an ANOVA test contrasting absolute RNA expression between pigs with regressing, progressing and without tumors was significant for TYR, TACSTD1, MATP, GPNMB and CYP4A22, with P-values of 0.034, 0.015, 0.007, 0.050 and 0.022, respectively.

Keywords

melanomametastasisgene expressionSinclair swine
Type
Full Paper
Information
animal , Volume 6 , Issue 2 , 03 January 2012 , pp. 179 - 192
Copyright
Copyright © The Animal Consortium 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alaoui-Jamali, MA, Dupre, I, Qiang, H 2004. Prediction of drug sensitivity and drug resistance in cancer by transcriptional and proteomic profiling. Drug Resistance Updates 7, 245–255.CrossRefGoogle ScholarPubMed
Altieri, DC 2003. Validating survivin as a cancer therapeutic target. Nature Reviews Cancer 3, 46–54.CrossRefGoogle ScholarPubMed
Altschul, SF, Madden, TL, Schäffer, AA, Zhang, J, Zhang, Z, Miller, W, Lipman, DJ 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research 25, 3389–3402.CrossRefGoogle ScholarPubMed
Angel, P, Karin, M 1991. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochimica et Biophysica Acta 1072, 129–157.Google ScholarPubMed
Barrier, A, Lemoine, A, Boelle, PY, Tse, C, Brault, D, Chiappini, F, Breittschneider, J, Lacaine, F, Houry, S, Huguier, M, Van der Laan, MJ, Speed, T, Debuire, B, Flahault, A, Dudoit, S 2005. Colon cancer prognosis prediction by gene expression profiling. Oncogene 24, 6155–6164.CrossRefGoogle ScholarPubMed
Battyani, Z, Xerri, L, Hassoun, J, Bonerandi, JJ, Grob, JJ 1993. Tyrosinase gene expression in human tissues. Pigment Cell Research 6, 400–405.CrossRefGoogle ScholarPubMed
Bittner, M, Meltzer, P, Chen, Y, Jiang, Y, Seftor, E, Hendrix, M, Radmacher, M, Simon, R, Yakhini, Z, Ben-Dor, A, Sampas, N, Dougherty, E, Wang, E, Marincola, F, Gooden, C, Lueders, J, Glatfelter, A, Pollock, P, Carpten, J, Gillanders, E, Leja, D, Dietrich, K, Beaudry, C, Berens, M, Alberts, D, Sondak, V 2000. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406, 536–540.CrossRefGoogle ScholarPubMed
Bohmann, D, Bos, TJ, Admon, A, Nishimura, T, Vogt, PK, Tjian, R 1987. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 238, 1386–1392.CrossRefGoogle ScholarPubMed
Chandra, D, Liu, JW, Tang, DG 2002. Early mitochondrial activation and cytochrome c upregulation during apoptosis. Journal of Biological Chemistry 277, 50842–50854.CrossRefGoogle ScholarPubMed
Chawla-Sarkar, M, Bae, SI, Reu, FJ, Jacobs, BS, Lindner, DJ, Borden, EC 2004. Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis. Cell Death and Differentiation 11, 915–923.CrossRefGoogle ScholarPubMed
Cheng, J, Yang, J, Xia, Y, Karin, M, Su, B 2000. Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation. Molecular and Cellular Biology 20, 2334–2342.CrossRefGoogle ScholarPubMed
Clarke, PA, te Poele, R, Workman, P 2004. Gene expression microarray technologies in the development of new therapeutic agents. European Journal of Cancer 40, 2560–2591.CrossRefGoogle ScholarPubMed
Das Gupta, TK, Ronan, SG, Beattie, CW, Shilkaitis, A, Amoss, MS Jr 1989. Comparative histopathology of porcine and human cutaneous melanoma. Pediatric Dermatology 6, 289–299.CrossRefGoogle ScholarPubMed
Eisen, MB, Brown, PO 1999. DNA arrays for analysis of gene expression. Methods in Enzymology 303, 179–205.CrossRefGoogle ScholarPubMed
Giltay, R, Kostka, G, Timpl, R 1997. Sequence and expression of a novel member (LTBP-4) of the family of latent transforming growth factor-beta binding proteins. FEBS Letters 411, 164–168.CrossRefGoogle ScholarPubMed
Gomez-Raya, L, Okomo-Adhiambo, M, Beattie, C, Osborne, K, Rink, A, Rauw, WM 2007. Modeling inheritance of malignant melanoma with DNA markers in Sinclair swine. Genetics 176, 585–597.CrossRefGoogle ScholarPubMed
Gomez-Raya, L, Amoss, MS, Da, Y, Beattie, CW, Smith, D, Ash, O, Rauw, WM 2009. Role of inbreeding, selection on the incidence of cutaneous malignant melanoma in Sinclair swine. Journal of Animal Breeding and Genetics 126, 242–249.CrossRefGoogle ScholarPubMed
Gong, J, Chen, N, Zhou, Q, Yang, B, Wang, Y, Wang, X 2005. Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus, but similarly in primary and metastatic melanomas. Journal of Clinical Pathology 58, 1081–1085.CrossRefGoogle ScholarPubMed
Greene, JF, Townsend, JS, Amoss, MS 1994. Histopathology of regression in Sinclair swine model of melanoma. Laboratory Investigation 71, 17–24.Google ScholarPubMed
Greene, JF Jr, Morgan, CD, Rao, A, Amoss, MS Jr, Arguello, F 1997. Regression by differentiation in the Sinclair swine model of cutaneous melanoma. Melanoma Research 7, 471–477.Google ScholarPubMed
Haqq, C, Nosrati, M, Sudilovsky, D, Crothers, J, Khodabakhsh, D, Pulliam, BL, Federman, S, Miller, JR III, Allen, RE, Singer, MI et al. 2005. The gene expression signatures of melanoma progression. Proceedings of the National Academy of Sciences of the United States of America 102, 6092–6097.CrossRefGoogle ScholarPubMed
Hoek, K, Rimm, DL, Williams, KR, Zhao, H, Ariyan, S, Lin, A, Kluger, HM, Berger, AJ, Cheng, E, Trombetta, ES et al. 2004. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Research 64, 5270–5282.CrossRefGoogle ScholarPubMed
Hook, RR Jr, Aultman, MD, Adelstein, EH, Oxenhandler, RW, Millikan, LE, Middleton, C 1979. Influence of selective breeding on the incidence of melanomas in Sinclair miniature swine. International Journal of Cancer 24, 668–672.CrossRefGoogle ScholarPubMed
Huang, Y, Sadee, W 2003. Drug sensitivity and resistance genes in cancer chemotherapy: a chemogenomics approach. Drug Discovery Today 8, 356–363.CrossRefGoogle ScholarPubMed
Ivanov, VN, Bhoumik, A, Ronai, Z 2003. Death receptors and melanoma resistance to apoptosis. Oncogene 22, 3152–3161.CrossRefGoogle ScholarPubMed
Jager, D, Stockert, E, Jager, E, Gure, AO, Scanlan, MJ, Knuth, A, Old, LJ, Chen, YT 2000. Serological cloning of a melanocyte rab guanosine 5′-triphosphate-binding protein and a chromosome condensation protein from a melanoma complementary DNA library. Cancer Research 60, 3584–3591.Google Scholar
James, K, Eisenhauer, E, Christian, M, Terenziani, M, Vena, D, Muldal, A, Therasse, P 1999. Measuring response in solid tumors: unidimensional versus bidimensional measurement. Journal of the National Cancer Institute 91, 523–528.CrossRefGoogle ScholarPubMed
Kawakami, Y, Robbins, PF, Wang, RF, Parkhurst, M, Kang, X, Rosenberg, SA 1998. The use of melanosomal proteins in the immunotherapy of melanoma. Journal of Immunotherapy 21, 237–246.CrossRefGoogle ScholarPubMed
Kwon, BS 1993. Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family. Journal of Investigative Dermatology 100, 134S–140S.CrossRefGoogle ScholarPubMed
LaCasse, EC, Baird, S, Korneluk, RG, MacKenzie, AE 1998. The inhibitors of apoptosis IAPs and their emerging role in cancer. Oncogene 17, 3247–3259.CrossRefGoogle ScholarPubMed
Leslie, MC, Zhao, YJ, Lachman, LB, Hwu, P, Bar-Eli, M 2007. Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastasis. Gene Therapy 14, 316–323.CrossRefGoogle ScholarPubMed
Lewis, TB, Robison, JE, Bastien, R, Milash, B, Boucher, K, Samlowski, WE, Leachman, SA, Dirk Noyes, R, Wittwer, CT, Perreard, L, Bernard, PS 2005. Molecular classification of melanoma using real-time quantitative reverse transcriptase-polymerase chain reaction. Cancer 104, 1678–1686.CrossRefGoogle ScholarPubMed
Li, H, Niederkorn, JY, Neelam, S, Alizadeh, H 2005. Resistance and susceptibility of human uveal melanoma cells to TRAIL-induced apoptosis. Archives of Ophthalmology 123, 654–661.CrossRefGoogle ScholarPubMed
Luo, J, Duggan, DJ, Chen, Y, Sauvageot, J, Ewing, CM, Bittner, ML, Trent, JM, Isaacs, WB 2001. Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Cancer Research 61, 4683–4688.Google ScholarPubMed
Mariadason, JM, Arango, D, Shi, Q, Wilson, AJ, Corner, GA, Nicholas, C, Aranes, MJ, Lesser, M, Schwartz, EL, Augenlicht, LH 2003. Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin. Cancer Research 63, 8791–8812.Google ScholarPubMed
Minitab 15. Minitab. Inc., State College, PA.Google Scholar
Misfeldt, ML, Grimm, DR 1994. Sinclair miniature swine: an animal model of human melanoma. Veterinary Immunology and Immunopathology 43, 167–175.CrossRefGoogle ScholarPubMed
Mitas, M, Cole, DJ, Hoover, L, Fraig, MM, Mikhitarian, K, Block, MI, Hoffman, BJ, Hawes, RH, Gillanders, WE, Wallace, MB 2003. Real-time reverse transcription-PCR detects KS1/4 mRNA in mediastinal lymph nodes from patients with non-small cell lung cancer. Clinical Chemistry 49, 312–325.CrossRefGoogle ScholarPubMed
Nordlund, JJ, Boissy, RE, Hearing, VJ, King, L, Ortonne, JP ed. 1998. The pigmentary system: physiology and pathophysiology. Oxford University Press, New York, NY.Google Scholar
Overwijk, WW, Lee, DS, Surman, DR, Irvine, KR, Touloukian, CE, Chan, CC, Carroll, MW, Moss, B, Rosenberg, SA, Restifo, NP 1999. Vaccination with a recombinant vaccinia virus encoding a ‘self’ antigen induces autoimmune vitiligo and tumor cell destruction in mice: requirement for CD4+ T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 96, 2982–2987.CrossRefGoogle ScholarPubMed
Parkhurst, MR, Fitzgerald, EB, Southwood, S, Sette, A, Rosenberg, SA, Kawakami, Y 1998. Identification of a shared HLA-A*0201-restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 TRP2. Cancer Research 58, 4895–4901.Google ScholarPubMed
Perez, RP, Zhang, P, Bosserhoff, AK, Buettner, R, Abu-Hadid, M 2000. Expression of melanoma inhibitory activity in melanoma and nonmelanoma tissue specimens. Human Pathology 31, 1381–1388.CrossRefGoogle ScholarPubMed
Pfaffl, MW, Horgan, G, Dempfle, L 2002. Relative Expression Software Tool REST© for group wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research 30, E36.Google Scholar
Rishi, AK, Zhang, L, Boyanapalli, M, Wali, A, Mohammad, RM, Yu, Y, Fontana, JA, Hatfield, JS, Dawson, MI, Majumdar, APN, Reichert, U 2003. Identification and characterization of a cell cycle and apoptosis regulatory protein-1 as a novel mediator of apoptosis signaling by retinoid CD437. The Journal of Biological Chemistry 278, 33422–33435.CrossRefGoogle ScholarPubMed
Robbins, PF, El-Gamil, M, Li, YF, Topalian, SL, Rivoltini, L, Sakaguchi, K, Appella, E, Kawakami, Y, Rosenberg, SA 1995. Cloning of a new gene encoding an antigen recognized by melanoma-specific HLA-A24-restricted tumor-infiltrating lymphocytes. The Journal of Immunology 154, 5944–5950.CrossRefGoogle ScholarPubMed
Sanjo, H, Kawai, T, Akira, S 1998. DRAKs, novel serine/threonine kinases related to death-associated protein kinase that trigger apoptosis. Journal of Biological Chemistry 273, 29066–29071.CrossRefGoogle ScholarPubMed
Savas, U, Hsu, MH, Johnson, EF 2003. Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone. Archives of Biochemistry and Biophysics 409, 212–220.Google ScholarPubMed
Simon, B, Podolsky, DK, Moldenhauer, G, Isselbacher, KJ, Gattoni-Celli, S, Brand, SJ 1990. Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein. Proceedings of the National Academy of Sciences of the United States of America 87, 2755–2759.CrossRefGoogle ScholarPubMed
Solano, F, Martínez-Esparza, M, Jiménez-Cervantes, C, Hill, SP, Lozano, JA, García-Borrón, JC 2000. New insights on the structure of the mouse silver locus and on the function of silver protein. Pigment Cell Research 13, 118–124.CrossRefGoogle ScholarPubMed
Takaoka, A, Hinoda, Y, Sato, S, Itoh, F, Adachi, M, Hareyama, M, Imai, K 1998. Reduced invasive and metastatic potentials of KAI1-transfected melanoma cells. Cancer Science 89, 397–404.Google ScholarPubMed
Talantov, D, Mazumder, A, Yu, JX, Briggs, T, Jiang, Y, Backus, J, Atkins, D, Wang, Y 2005. Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clinical Cancer Research 11, 7234–7242.CrossRefGoogle Scholar
Tissot, RG, Beattie, CW, Amoss, MS Jr 1987. Inheritance of Sinclair swine cutaneous malignant melanoma. Cancer Research 47, 5542–5545.Google ScholarPubMed
Tripathi, RK, Hearing, VJ, Urabe, K, Aroca, P, Spritz, RA 1992. Mutational mapping of the catalytic activities of human tyrosinase. Journal of Biological Chemistry 267, 23707–23712.CrossRefGoogle ScholarPubMed
Tsai, S, Cassady, JP, Freking, BA, Nonneman, DJ, Rohrer, GA, Piedrahita, JA 2006. Annotation of the Affymetrix porcine genome microarray. Animal Genetics 37, 423–424.CrossRefGoogle ScholarPubMed
Ullman, KS, Northrop, JP, Verweij, CL, Crabtree, GR 1990. Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: the missing link. Annual Review of Immunology 8, 421–452.CrossRefGoogle Scholar
van den Brûle, FA, Buicu, C, Baldet, M, Sobel, ME, Cooper, DN, Marschal, P, Castronovo, V 1995. Galectin-1 modulates human melanoma cell adhesion to laminin. Biochemical and Biophysical Research Communications 209, 760–767.CrossRefGoogle ScholarPubMed
Velasco-Miguel, S, Buckbinder, L, Jean, P, Gelbert, L, Talbott, R, Laidlaw, J, Seizinger, B, Kley, N 1999. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. Oncogene 18, 127–137.CrossRefGoogle ScholarPubMed
Wallace, MBBlock, MI, Gillanders, W, Ravenel, J, Hoffman, BJ, Reed, CE, Fraig, M, Cole, D, Mitas, M 2005. Accurate molecular detection of non-small cell lung cancer metastases in mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration. Chest 127, 430–437.CrossRefGoogle ScholarPubMed
Wang, Y, Jatkoe, T, Zhang, Y, Mutch, MG, Talantov, D, Jiang, J, McLeod, HL, Atkins, D 2004. Gene expression profiles and molecular markers to predict recurrence of Dukes’ B colon cancer. Journal of Clinical Oncology 22, 1564–1571.CrossRefGoogle ScholarPubMed
Watson-Hurst, K, Becker, D 2006. The role of N-cadherin, MCAM and beta3 integrin in melanoma progression, proliferation, migration and invasion. Cancer Biology and Therapy 5, 1375–1382.CrossRefGoogle ScholarPubMed
Weterman, MAJ, Ajubi, N, van Dinter, IMR, Degen, WGJ, van Muijen, GNP, Ruiter, DJ, Bloemers, HPJ 1995. Nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. International Journal of Cancer 60, 73–81.CrossRefGoogle ScholarPubMed
Yuen, T, Wurmbach, E, Pfeffer, RL, Ebersole, BJ, Sealfon, SC 2002. Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays. Nucleic Acids Research 30, e48.CrossRefGoogle ScholarPubMed
Zhou, Y, Dai, DL, Martinka, M, Su, M, Zhang, Y, Campos, EI, Dorocicz, I, Tang, L, Huntsman, D, Nelson, C, Ho, V, Li, G 2005. Osteopontin expression correlates with melanoma invasion. Journal of Investigative Dermatology 124, 1044–1052.Google ScholarPubMed