Skip to main content
Erschienen in: Medical Oncology 2/2012

01.06.2012 | Original Paper

The overexpression of AP-4 as a prognostic indicator for gastric carcinoma

verfasst von: Liu Xinghua, Zhang Bo, Guo Yan, Wu Lei, Wu Changyao, Liang Qi, Ye Lin, Tao Kaixiong, Wang Guobin, Chen Jianying

Erschienen in: Medical Oncology | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

As a transcription factor belonging to the basic helix-loop-helix leucine-zipper subgroup, AP-4 can control target gene expression by altering cell signal transduction, and regulate growth, development, and cell apoptosis. Under pathological circumstances, it is involved in tumorigenesis. Herein, immunohistochemistry and real-time PCR were used to detect the transcription factor AP-4 expression in gastric cancer, and these data were examined for correlation with histology, pTNM stage, and prognosis. The AP-4 expression rate was 83.67% in a total of 98 gastric cancer tissues, which was significantly higher than 40.91% in non-neoplastic tissues; AP-4 mRNA relative expression shows a significant difference between gastric cancer and normal tissues, and AP-4 expression has a significantly positive correlation with the depth of tumor invasion (P < 0.0001), degree of tumor differentiation (P = 0.0058), lymph node metastasis (P = 0.0255), and pTNM stage (P = 0.001). Survival analysis showed that AP-4-positive patients’ median survival time (12.60 months) was significantly shorter than that (41.40 months) of AP-4-negative patients. AP-4 expression in gastric cancer is associated with clinicopathological parameters of gastric cancer, such as differentiation, lymph node metastasis, depth of invasion (P = 0.0010), and pTNM stage. What’s more, AP-4 overexpression indicated a worse prognosis for patients. So AP-4 may be a molecular marker to predict the progression and prognosis of the tumor.
Literatur
1.
Zurück zum Zitat Correia M, Machado JC, Ristimaki A. Basic aspects of gastric cancer. Helicobacter. 2009;14(Suppl 1):36–40.PubMedCrossRef Correia M, Machado JC, Ristimaki A. Basic aspects of gastric cancer. Helicobacter. 2009;14(Suppl 1):36–40.PubMedCrossRef
2.
Zurück zum Zitat Wu K, Nie Y, Guo C, Chen Y, Ding J, Fan D. Molecular basis of therapeutic approaches to gastric cancer. J Gastroenterol Hepatol. 2009;24(1):37–41. Wu K, Nie Y, Guo C, Chen Y, Ding J, Fan D. Molecular basis of therapeutic approaches to gastric cancer. J Gastroenterol Hepatol. 2009;24(1):37–41.
3.
Zurück zum Zitat Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F, Van Cutsem E. Gastric cancer. Crit Rev Oncol Hematol. 2009;71(2):127–64.PubMedCrossRef Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F, Van Cutsem E. Gastric cancer. Crit Rev Oncol Hematol. 2009;71(2):127–64.PubMedCrossRef
4.
5.
Zurück zum Zitat Massari ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol. 2000;20(2):429–40.PubMedCrossRef Massari ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol. 2000;20(2):429–40.PubMedCrossRef
6.
Zurück zum Zitat Grau R, Punzon C, Fresno M, Iniguez MA. Peroxisome-proliferator-activated receptor alpha agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1. Biochem J. 2006;395(1):81–8.PubMedCrossRef Grau R, Punzon C, Fresno M, Iniguez MA. Peroxisome-proliferator-activated receptor alpha agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1. Biochem J. 2006;395(1):81–8.PubMedCrossRef
7.
Zurück zum Zitat Atchley WR, Fitch WM. A natural classification of the basic helix-loop-helix class of transcription factors. Proc Natl Acad Sci USA. 1997;94(10):5172–6.PubMedCrossRef Atchley WR, Fitch WM. A natural classification of the basic helix-loop-helix class of transcription factors. Proc Natl Acad Sci USA. 1997;94(10):5172–6.PubMedCrossRef
8.
Zurück zum Zitat Lee SU, Song HO, Lee W, Singaravelu G, Yu JR, Park WY. Identification and characterization of a putative basic helix-loop-helix (bHLH) transcription factor interacting with calcineurin in C. elegans. Mol Cells. 2009;28(5):455–61. Lee SU, Song HO, Lee W, Singaravelu G, Yu JR, Park WY. Identification and characterization of a putative basic helix-loop-helix (bHLH) transcription factor interacting with calcineurin in C. elegans. Mol Cells. 2009;28(5):455–61.
9.
Zurück zum Zitat Mermod N, Williams TJ, Tjian R. Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 1988;332(6164):557–61.PubMedCrossRef Mermod N, Williams TJ, Tjian R. Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 1988;332(6164):557–61.PubMedCrossRef
10.
Zurück zum Zitat Hu YF, Luscher B, Admon A, Mermod N, Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990;4(10):1741–52.PubMedCrossRef Hu YF, Luscher B, Admon A, Mermod N, Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990;4(10):1741–52.PubMedCrossRef
11.
Zurück zum Zitat Jung P, Menssen A, Mayr D, Hermeking H. AP4 encodes a c-MYC-inducible repressor of p21. Proc Natl Acad Sci USA. 2008;105(39):15046–51.PubMedCrossRef Jung P, Menssen A, Mayr D, Hermeking H. AP4 encodes a c-MYC-inducible repressor of p21. Proc Natl Acad Sci USA. 2008;105(39):15046–51.PubMedCrossRef
13.
Zurück zum Zitat Cui Y, Narayanan CS, Zhou J, Kumar A. Exon-I is involved in positive as well as negative regulation of human angiotensinogen gene expression. Gene. 1998;224(1–2):97–107.PubMedCrossRef Cui Y, Narayanan CS, Zhou J, Kumar A. Exon-I is involved in positive as well as negative regulation of human angiotensinogen gene expression. Gene. 1998;224(1–2):97–107.PubMedCrossRef
14.
Zurück zum Zitat Wang R, Zhang YW, Zhang X, Liu R, Hong S, Xia K, et al. Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxia. FASEB J. 2006;20(8):1275–7.PubMedCrossRef Wang R, Zhang YW, Zhang X, Liu R, Hong S, Xia K, et al. Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxia. FASEB J. 2006;20(8):1275–7.PubMedCrossRef
15.
Zurück zum Zitat Tsujimoto K, Ono T, Sato M, Nishida T, Oguma T, Tadakuma T. Regulation of the expression of caspase-9 by the transcription factor activator protein-4 in glucocorticoid-induced apoptosis. J Biol Chem. 2005;280(30):27638–44.PubMedCrossRef Tsujimoto K, Ono T, Sato M, Nishida T, Oguma T, Tadakuma T. Regulation of the expression of caspase-9 by the transcription factor activator protein-4 in glucocorticoid-induced apoptosis. J Biol Chem. 2005;280(30):27638–44.PubMedCrossRef
16.
Zurück zum Zitat Kim MY, Jeong BC, Lee JH, Kee HJ, Kook H, Kim NS, et al. A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells. Proc Natl Acad Sci USA. 2006;103(35):13074–9.PubMedCrossRef Kim MY, Jeong BC, Lee JH, Kee HJ, Kook H, Kim NS, et al. A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells. Proc Natl Acad Sci USA. 2006;103(35):13074–9.PubMedCrossRef
17.
Zurück zum Zitat Unk I, Kiss-Toth E, Boros I. Transcription factor AP-4 participates in activation of bovine leukemia virus long terminal repeat by p34 tax. Nucleic Acids Res. 1994;22(23):4872–5.PubMedCrossRef Unk I, Kiss-Toth E, Boros I. Transcription factor AP-4 participates in activation of bovine leukemia virus long terminal repeat by p34 tax. Nucleic Acids Res. 1994;22(23):4872–5.PubMedCrossRef
18.
Zurück zum Zitat Glahder JA, Hansen CN, Vinther J, Madsen BS, Norrild B. A promoter within the E6 ORF of human papillomavirus type 16 contributes to the expression of the E7 oncoprotein from a monocistronic mRNA. J Gen Virol. 2003;84(Pt 12):3429–41.PubMedCrossRef Glahder JA, Hansen CN, Vinther J, Madsen BS, Norrild B. A promoter within the E6 ORF of human papillomavirus type 16 contributes to the expression of the E7 oncoprotein from a monocistronic mRNA. J Gen Virol. 2003;84(Pt 12):3429–41.PubMedCrossRef
19.
Zurück zum Zitat Fodor E, Weinrich SL, Meister A, Mermod N, Rutter WJ. A pancreatic exocrine cell factor and AP4 bind overlapping sites in the amylase 2A enhancer. Biochemistry. 1991;30(33):8102–8.PubMedCrossRef Fodor E, Weinrich SL, Meister A, Mermod N, Rutter WJ. A pancreatic exocrine cell factor and AP4 bind overlapping sites in the amylase 2A enhancer. Biochemistry. 1991;30(33):8102–8.PubMedCrossRef
20.
Zurück zum Zitat Cao J, Tang M, Li WL, Xie J, Du H, Tang WB, et al. Upregulation of activator protein-4 in human colorectal cancer with metastasis. Int J Surg Pathol. 2009;17(1):16–21.PubMed Cao J, Tang M, Li WL, Xie J, Du H, Tang WB, et al. Upregulation of activator protein-4 in human colorectal cancer with metastasis. Int J Surg Pathol. 2009;17(1):16–21.PubMed
21.
Zurück zum Zitat Lin TX, Huang J, Huang H, Cai QQ, Xu KW, Yin XB, et al. Identification of response element gene sequence for non-steroid hormone transcription factors for the activation and up-regulation of L-plastin expression in prostate cancer. Zhonghua Nan Ke Xue. 2005;11(10):731–4.PubMed Lin TX, Huang J, Huang H, Cai QQ, Xu KW, Yin XB, et al. Identification of response element gene sequence for non-steroid hormone transcription factors for the activation and up-regulation of L-plastin expression in prostate cancer. Zhonghua Nan Ke Xue. 2005;11(10):731–4.PubMed
22.
Zurück zum Zitat Zheng L, Weng M, He J, Yang X, Jiang G, Tong Q. Expression of resistin-like molecule beta in gastric cancer: its relationship with clinicopathological parameters and prognosis. Virchows Arch. 2010;456(1):53–63.PubMedCrossRef Zheng L, Weng M, He J, Yang X, Jiang G, Tong Q. Expression of resistin-like molecule beta in gastric cancer: its relationship with clinicopathological parameters and prognosis. Virchows Arch. 2010;456(1):53–63.PubMedCrossRef
23.
Zurück zum Zitat Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48(13):3554–60.PubMed Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48(13):3554–60.PubMed
24.
Zurück zum Zitat Akyurek N, Akyol G, Dursun A, Yamac D, Gunel N. Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis. Pathol Res Pract. 2002;198(10):665–74.PubMedCrossRef Akyurek N, Akyol G, Dursun A, Yamac D, Gunel N. Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis. Pathol Res Pract. 2002;198(10):665–74.PubMedCrossRef
25.
Zurück zum Zitat Edmondson DG, Olson EN. A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989;3(5):628–40.PubMedCrossRef Edmondson DG, Olson EN. A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989;3(5):628–40.PubMedCrossRef
26.
Zurück zum Zitat Lassar AB, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, et al. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell. 1989;58(5):823–31.PubMedCrossRef Lassar AB, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, et al. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell. 1989;58(5):823–31.PubMedCrossRef
27.
Zurück zum Zitat Ludwig SR, Habera LF, Dellaporta SL, Wessler SR. Lc, a member of the maize R gene family responsible for tissue-specific anthocyanin production, encodes a protein similar to transcriptional activators and contains the myc-homology region. Proc Natl Acad Sci USA. 1989;86(18):7092–6.PubMedCrossRef Ludwig SR, Habera LF, Dellaporta SL, Wessler SR. Lc, a member of the maize R gene family responsible for tissue-specific anthocyanin production, encodes a protein similar to transcriptional activators and contains the myc-homology region. Proc Natl Acad Sci USA. 1989;86(18):7092–6.PubMedCrossRef
28.
Zurück zum Zitat Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989;58(3):537–44.PubMedCrossRef Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989;58(3):537–44.PubMedCrossRef
29.
Zurück zum Zitat Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989;56(5):777–83.PubMedCrossRef Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989;56(5):777–83.PubMedCrossRef
30.
Zurück zum Zitat Bae Y, Kim H, Namgoong H, Baek M, Lee J, Hwang D, et al. Characterization of microsatellite markers adjacent to AP-4 on chromosome 16p13.3. Mol Cell Probes. 2001;15(5):313–5. Bae Y, Kim H, Namgoong H, Baek M, Lee J, Hwang D, et al. Characterization of microsatellite markers adjacent to AP-4 on chromosome 16p13.3. Mol Cell Probes. 2001;15(5):313–5.
31.
Zurück zum Zitat Buechler S. Low expression of a few genes indicates good prognosis in estrogen receptor positive breast cancer. BMC Cancer. 2009;9:243.PubMedCrossRef Buechler S. Low expression of a few genes indicates good prognosis in estrogen receptor positive breast cancer. BMC Cancer. 2009;9:243.PubMedCrossRef
32.
Zurück zum Zitat Xi YG, Ding KY, Su XL, Chen DF, You WC, Shen Y, et al. p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions. Carcinogenesis. 2004;25(11):2201–6.PubMedCrossRef Xi YG, Ding KY, Su XL, Chen DF, You WC, Shen Y, et al. p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions. Carcinogenesis. 2004;25(11):2201–6.PubMedCrossRef
33.
Zurück zum Zitat Seo YH, Joo YE, Choi SK, Rew JS, Park CS, Kim SJ. Prognostic significance of p21 and p53 expression in gastric cancer. Korean J Intern Med. 2003;18(2):98–103.PubMed Seo YH, Joo YE, Choi SK, Rew JS, Park CS, Kim SJ. Prognostic significance of p21 and p53 expression in gastric cancer. Korean J Intern Med. 2003;18(2):98–103.PubMed
34.
Zurück zum Zitat Hajdu J, Kozma L, Kiss I, Szentkereszty Z, Szakall S, Ember I. Is the presence of distant metastasis associated with c-myc amplification in gastric cancer? Acta Chir Hung. 1997;36(1–4):119–21.PubMed Hajdu J, Kozma L, Kiss I, Szentkereszty Z, Szakall S, Ember I. Is the presence of distant metastasis associated with c-myc amplification in gastric cancer? Acta Chir Hung. 1997;36(1–4):119–21.PubMed
35.
Zurück zum Zitat Onoda N, Maeda K, Chung YS, Yano Y, Matsui-Yuasa I, Otani S, et al. Overexpression of c-myc messenger RNA in primary and metastatic lesions of carcinoma of the stomach. J Am Coll Surg. 1996;182(1):55–9.PubMed Onoda N, Maeda K, Chung YS, Yano Y, Matsui-Yuasa I, Otani S, et al. Overexpression of c-myc messenger RNA in primary and metastatic lesions of carcinoma of the stomach. J Am Coll Surg. 1996;182(1):55–9.PubMed
36.
Zurück zum Zitat Kouraklis G, Katsoulis IE, Theocharis S, Tsourouflis G, Xipolitas N, Glinavou A, et al. Does the expression of cyclin E, pRb, and p21 correlate with prognosis in gastric adenocarcinoma? Dig Dis Sci. 2009;54(5):1015–20.PubMedCrossRef Kouraklis G, Katsoulis IE, Theocharis S, Tsourouflis G, Xipolitas N, Glinavou A, et al. Does the expression of cyclin E, pRb, and p21 correlate with prognosis in gastric adenocarcinoma? Dig Dis Sci. 2009;54(5):1015–20.PubMedCrossRef
37.
Zurück zum Zitat Han S, Kim HY, Park K, Cho HJ, Lee MS, Kim HJ, et al. c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer. J Korean Med Sci. 1999;14(5):526–30.PubMed Han S, Kim HY, Park K, Cho HJ, Lee MS, Kim HJ, et al. c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer. J Korean Med Sci. 1999;14(5):526–30.PubMed
Metadaten
Titel
The overexpression of AP-4 as a prognostic indicator for gastric carcinoma
verfasst von
Liu Xinghua
Zhang Bo
Guo Yan
Wu Lei
Wu Changyao
Liang Qi
Ye Lin
Tao Kaixiong
Wang Guobin
Chen Jianying
Publikationsdatum
01.06.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9845-8

Weitere Artikel der Ausgabe 2/2012

Medical Oncology 2/2012 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.