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Molecular Cancer
Published in: Molecular Cancer 1/2008

Open Access 01-12-2008 | Research

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

Authors: Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J Liao

Published in: Molecular Cancer | Issue 1/2008

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Abstract

Background

Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials.

Results

Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples.

Conclusion

We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.
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Literature
1.
Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, Iacobuzio-Donahue CA, Maitra A, Goggins M, Canto MI: Pancreatic cancer. Curr Probl Cancer. 2002, 26 (4): 176-275.CrossRefPubMed
2.
Schleger C, Verbeke C, Hildenbrand R, Zentgraf H, Bleyl U: c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: incidence, mechanisms, and clinical significance. Mod Pathol. 2002, 15 (4): 462-469.CrossRefPubMed
3.
Mahlamaki EH, Barlund M, Tanner M, Gorunova L, Hoglund M, Karhu R, Kallioniemi A: Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Genes Chromosomes Cancer. 2002, 35 (4): 353-358.CrossRefPubMed
4.
Yamada H, Sakamoto H, Taira M, Nishimura S, Shimosato Y, Terada M, Sugimura T: Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes. Jpn J Cancer Res. 1986, 77 (4): 370-375.PubMed
5.
Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD, Brinster RL: Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci USA. 1991, 88 (1): 93-97.PubMedCentralCrossRefPubMed
6.
Liao DJ, Wang Y, Wu J, Adsay NV, Grignon D, Khanani F, Sarkar FH: Characterization of pancreatic lesions from MT-tgfalpha, Ela-myc and MT-tgfalpha/Ela-myc single and double transgenic mice. J Carcinog. 2006, 5: 19-PubMedCentralCrossRefPubMed
7.
Liao JD, Adsay NV, Khannani F, Grignon D, Thakur A, Sarkar FH: Histological complexities of pancreatic lesions from transgenic mouse models are consistent with biological and morphological heterogeneity of human pancreatic cancer. Histol Histopathol. 2007, 22 (6): 661-676.PubMedCentralPubMed
8.
9.
Kleeff J, Friess H, Berberat PO, Martignoni ME, Z'Graggen K, Buchler MW: Pancreatic cancer – new aspects of molecular biology research. Swiss Surg. 2000, 6 (5): 231-234.CrossRefPubMed
10.
Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato N, Parker A, Ashfaq R: Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol. 2003, 162 (4): 1151-1162.PubMedCentralCrossRefPubMed
11.
Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, Meyer R, Walter K, Berg K, Hollingsworth MA, Cameron JL: Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am J Pathol. 2002, 160 (4): 1239-1249.PubMedCentralCrossRefPubMed
12.
Maacke H, Jost K, Opitz S, Miska S, Yuan Y, Hasselbach L, Luttges J, Kalthoff H, Sturzbecher HW: DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocarcinoma. Oncogene. 2000, 19 (23): 2791-2795.CrossRefPubMed
13.
Lynch HT, Deters CA, Snyder CL, Lynch JF, Villeneuve P, Silberstein J, Martin H, Narod SA, Brand RE: BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet. 2005, 158 (2): 119-125.CrossRefPubMed
14.
Mahlamaki EH, Kauraniemi P, Monni O, Wolf M, Hautaniemi S, Kallioniemi A: High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer. Neoplasia. 2004, 6 (5): 432-439.PubMedCentralCrossRefPubMed
15.
Nakamura T, Fidler IJ, Coombes KR: Gene expression profile of metastatic human pancreatic cancer cells depends on the organ microenvironment. Cancer Res. 2007, 67 (1): 139-148.CrossRefPubMed
16.
Nakamura T, Furukawa Y, Nakagawa H, Tsunoda T, Ohigashi H, Murata K, Ishikawa O, Ohgaki K, Kashimura N, Miyamoto M: Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection. Oncogene. 2004, 23 (13): 2385-2400.CrossRefPubMed
17.
Soling A, Sackewitz M, Volkmar M, Schaarschmidt D, Jacob R, Holzhausen HJ, Rainov NG: Minichromosome maintenance protein 3 elicits a cancer-restricted immune response in patients with brain malignancies and is a strong independent predictor of survival in patients with anaplastic astrocytoma. Clin Cancer Res. 2005, 11 (1): 249-258.PubMed
18.
Sanada Y, Oue N, Mitani Y, Yoshida K, Nakayama H, Yasui W: Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol. 2006, 208 (5): 633-642.CrossRefPubMed
19.
Yonezawa S, Byrd JC, Dahiya R, Ho JJ, Gum JR, Griffiths B, Swallow DM, Kim YS: Differential mucin gene expression in human pancreatic and colon cancer cells. Biochem J. 1991, 276 (Pt 3): 599-605.PubMedCentralCrossRefPubMed
20.
Hollingsworth MA, Swanson BJ: Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004, 4 (1): 45-60.CrossRefPubMed
21.
Resar LM, Dolde C, Barrett JF, Dang CV: B-myc inhibits neoplastic transformation and transcriptional activation by c-myc. Mol Cell Biol. 1993, 13 (2): 1130-1136.PubMedCentralPubMed
22.
Griffith OL, Melck A, Jones SJ, Wiseman SM: Meta-analysis and meta-review of thyroid cancer gene expression profiling studies identifies important diagnostic biomarkers. J Clin Oncol. 2006, 24 (31): 5043-5051.CrossRefPubMed
23.
Moore LE, Fung ET, McGuire M, Rabkin CC, Molinaro A, Wang Z, Zhang F, Wang J, Yip C, Meng XY: Evaluation of apolipoprotein A1 and posttranslationally modified forms of transthyretin as biomarkers for ovarian cancer detection in an independent study population. Cancer Epidemiol Biomarkers Prev. 2006, 15 (9): 1641-1646.CrossRefPubMed
24.
Weinstein PS, Skinner M, Sipe JD, Lokich JJ, Zamcheck N, Cohen AS: Acute-phase proteins or tumour markers: the role of SAA, SAP, CRP and CEA as indicators of metastasis in a broad spectrum of neoplastic diseases. Scand J Immunol. 1984, 19 (3): 193-198.CrossRefPubMed
25.
Sato N, Fukushima N, Maitra A, Iacobuzio-Donahue CA, van Heek NT, Cameron JL, Yeo CJ, Hruban RH, Goggins M: Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas. Am J Pathol. 2004, 164 (3): 903-914.PubMedCentralCrossRefPubMed
26.
Lian Z, De Luca P, Di Cristofano A: Gene expression analysis reveals a signature of estrogen receptor activation upon loss of Pten in a mouse model of endometrial cancer. J Cell Physiol. 2006, 208 (2): 255-266.CrossRefPubMed
27.
Liu AY, Zhang H, Sorensen CM, Diamond DL: Analysis of prostate cancer by proteomics using tissue specimens. J Urol. 2005, 173 (1): 73-78.CrossRefPubMed
28.
Mauri P, Scarpa A, Nascimbeni AC, Benazzi L, Parmagnani E, Mafficini A, Della Peruta M, Bassi C, Miyazaki K, Sorio C: Identification of proteins released by pancreatic cancer cells by multidimensional protein identification technology: a strategy for identification of novel cancer markers. Faseb J. 2005, 19 (9): 1125-1127.PubMed
29.
Hansel DE, Rahman A, House M, Ashfaq R, Berg K, Yeo CJ, Maitra A: Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Clin Cancer Res. 2004, 10 (18 Pt 1): 6152-6158.CrossRefPubMed
30.
Karna E, Surazynski A, Orlowski K, Laszkiewicz J, Puchalski Z, Nawrat P, Palka J: Serum and tissue level of insulin-like growth factor-I (IGF-I) and IGF-I binding proteins as an index of pancreatitis and pancreatic cancer. Int J Exp Pathol. 2002, 83 (5): 239-245.PubMedCentralCrossRefPubMed
31.
32.
Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene. 2004, 23 (35): 5901-5911.CrossRefPubMed
33.
Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R, Shoemaker DD: Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science. 2003, 302 (5653): 2141-2144.CrossRefPubMed
34.
Pajares MJ, Ezponda T, Catena R, Calvo A, Pio R, Montuenga LM: Alternative splicing: an emerging topic in molecular and clinical oncology. Lancet Oncol. 2007, 8 (4): 349-357.CrossRefPubMed
35.
Srebrow A, Kornblihtt AR: The connection between splicing and cancer. J Cell Sci. 2006, 119 (Pt 13): 2635-2641.CrossRefPubMed
36.
37.
38.
Hayes GM, Carrigan PE, Beck AM, Miller LJ: Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Cancer Res. 2006, 66 (7): 3819-3827.CrossRefPubMed
39.
Zahler AM, Neugebauer KM, Lane WS, Roth MB: Distinct functions of SR proteins in alternative pre-mRNA splicing. Science. 1993, 260 (5105): 219-222.CrossRefPubMed
40.
Stickeler E, Kittrell F, Medina D, Berget SM: Stage-specific changes in SR splicing factors and alternative splicing in mammary tumorigenesis. Oncogene. 1999, 18 (24): 3574-3582.CrossRefPubMed
41.
Bailis JM, Forsburg SL: MCM proteins: DNA damage, mutagenesis and repair. Curr Opin Genet Dev. 2004, 14 (1): 17-21.CrossRefPubMed
42.
Hirano T: At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol. 2006, 7 (5): 311-322.CrossRefPubMed
43.
Amor DJ, Kalitsis P, Sumer H, Choo KH: Building the centromere: from foundation proteins to 3D organization. Trends Cell Biol. 2004, 14 (7): 359-368.CrossRefPubMed
44.
Khanna KK, Jackson SP: DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001, 27 (3): 247-254.CrossRefPubMed
45.
Kataoka H, Itoh H, Koono M: Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration. Pathol Int. 2002, 52 (2): 89-102.CrossRefPubMed
46.
Firth SM, Baxter RC: Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002, 23 (6): 824-854.CrossRefPubMed
47.
Perks CM, Newcomb PV, Norman MR, Holly JM: Effect of insulin-like growth factor binding protein-1 on integrin signalling and the induction of apoptosis in human breast cancer cells. J Mol Endocrinol. 1999, 22 (2): 141-150.CrossRefPubMed
48.
Jones JI, Doerr ME, Clemmons DR: Cell migration: interactions among integrins, IGFs and IGFBPs. Prog Growth Factor Res. 1995, 6 (2–4): 319-327.CrossRefPubMed
49.
Petrache I, Fijalkowska I, Zhen L, Medler TR, Brown E, Cruz P, Choe KH, Taraseviciene-Stewart L, Scerbavicius R, Shapiro L: A novel antiapoptotic role for alpha1-antitrypsin in the prevention of pulmonary emphysema. Am J Respir Crit Care Med. 2006, 173 (11): 1222-1228.PubMedCentralCrossRefPubMed
50.
Zelvyte I, Wallmark A, Piitulainen E, Westin U, Janciauskiene S: Increased plasma levels of serine proteinase inhibitors in lung cancer patients. Anticancer Res. 2004, 24 (1): 241-247.PubMed
51.
Trichopoulos D, Tzonou A, Kalapothaki V, Sparos L, Kremastinou T, Skoutari M: Alpha 1-antitrypsin and survival in pancreatic cancer. Int J Cancer. 1990, 45 (4): 685-686.CrossRefPubMed
52.
Tzonou A, Sparos L, Kalapothaki V, Zavitsanos X, Rebelakos A, Trichopoulos D: Alpha 1-antitrypsin and survival in hepatocellular carcinoma. Br J Cancer. 1990, 61 (1): 72-73.PubMedCentralCrossRefPubMed
53.
Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R: An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis. Br J Cancer. 1992, 65 (2): 300-302.PubMedCentralCrossRefPubMed
54.
Sun Z, Yang P: Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression. Lancet Oncol. 2004, 5 (3): 182-190.CrossRefPubMed
55.
Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R, Matsuura N, Murata A, Tomita N, Monden T, Ogawa M: Immunohistochemical analysis of pancreatic secretory trypsin inhibitor expression in pulmonary adenocarcinoma: its possible participation in scar formation of the tumor tissues. Tumour Biol. 1992, 13 (5–6): 299-307.CrossRefPubMed
56.
Thakur A, Xu H, Wang Y, Bollig A, Biliran H, Liao JD: The role of X-linked genes in breast cancer. Breast Cancer Res Treat. 2005, 93 (2): 135-143.CrossRefPubMed
57.
Oji Y, Nakamori S, Fujikawa M, Nakatsuka S, Yokota A, Tatsumi N, Abeno S, Ikeba A, Takashima S, Tsujie M: Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma. Cancer Sci. 2004, 95 (7): 583-7.CrossRefPubMed
Metadata
Title
Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice
Authors
Archana Thakur
Aliccia Bollig
Jiusheng Wu
Dezhong J Liao
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2008
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-7-11

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