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Published in: Journal of Experimental & Clinical Cancer Research 1/2008

Open Access 01-12-2008 | Research

Id-1: Regulator of EGFR and VEGF and potential target for colorectal cancer therapy

Authors: Ibrahim Meteoglu, Nezih Meydan, Muhan Erkus

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2008

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Abstract

Background

The helix-loop-helix transcription factor Id-1 (an inhibitor of differentiation and DNA binding) plays a role in development and progression of many tumours. Id-1 is known to exert its effects on the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). The aim of this study was to reveal whether there was a relationship between Id-1 and EGFR and VEGF in colorectal carcinoma.

Methods

Tumour and non-tumour tissue specimens from 46 cases of colorectal carcinoma were exposed to immunohistochemical staining for Id-1, EGFR and VEGF. The relationship between the degree of staining and tumour grade, tumour stage and all tumour markers was investigated.

Results

Tumour cells showed positive staining for Id-1 in 43 cases (93.5%), for EGFR in 41 cases (89%) and for VEGF in 42 cases (91%). There was a significant relation between the tumour grade and the degree of staining for Id-1, EGFR and VEGF. The relation between the tumour stage and the degree of staining for Id-1, EGFR and VEGF was also significant. There was a significant relation between Id-1 expression and EGFR and VEGF expressions. Non-tumoural tissue specimens were not stained with Id-1 and EGFR antibodies in any of the cases, but stained with VEGF antibody in 3 cases.

Conclusion

This study revealed that Id-1, EGFR and VEGF took part in development and progression of colorectal carcinomas and that Id-1 was associated with regulations of EGFR and VEGF. The results of this study support the idea that not only EGFR and VEGF but also Id-1 could be new targets in cancer treatment.
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Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRef Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRef
2.
go back to reference Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP: American Joint Committee on Cancer Prognostic Factors Consensus Conference:Colorectal Working Group. Cancer. 2000, 1;88: 1739-57. 10.1002/(SICI)1097-0142(20000401)88:7<1739::AID-CNCR30>3.0.CO;2-T.CrossRef Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP: American Joint Committee on Cancer Prognostic Factors Consensus Conference:Colorectal Working Group. Cancer. 2000, 1;88: 1739-57. 10.1002/(SICI)1097-0142(20000401)88:7<1739::AID-CNCR30>3.0.CO;2-T.CrossRef
3.
go back to reference Uberall I, Kolár Z, Trojanec R, Berkovcová J, Hajdúch M: The status and role of ErbB receptors in human cancer. Exp Mol Pathol. 2008, 84: 79-89. 10.1016/j.yexmp.2007.12.002.CrossRef Uberall I, Kolár Z, Trojanec R, Berkovcová J, Hajdúch M: The status and role of ErbB receptors in human cancer. Exp Mol Pathol. 2008, 84: 79-89. 10.1016/j.yexmp.2007.12.002.CrossRef
4.
go back to reference McKay JA, Murray LJ, Curran S, Ross VG, Clark C, Murray GI, Cassidy J, McLeod HL: Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer. 2002, 38: 2258-64. 10.1016/S0959-8049(02)00234-4.CrossRef McKay JA, Murray LJ, Curran S, Ross VG, Clark C, Murray GI, Cassidy J, McLeod HL: Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer. 2002, 38: 2258-64. 10.1016/S0959-8049(02)00234-4.CrossRef
5.
go back to reference Kopp R, Rothbauer E, Mueller E, Schildberg FW, Jauch KW, Pfeiffer A: Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels. Dis Colon Rectum. 2003, 46: 1391-9. 10.1007/s10350-004-6756-1.CrossRef Kopp R, Rothbauer E, Mueller E, Schildberg FW, Jauch KW, Pfeiffer A: Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels. Dis Colon Rectum. 2003, 46: 1391-9. 10.1007/s10350-004-6756-1.CrossRef
6.
go back to reference Kopp R, Rothbauer E, Ruge M, Arnholdt H, Spranger J, Muders M, Pfeiffer DG, Schildberg FW, Pfeiffer A: Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res. 2003, 162: 115-32.CrossRef Kopp R, Rothbauer E, Ruge M, Arnholdt H, Spranger J, Muders M, Pfeiffer DG, Schildberg FW, Pfeiffer A: Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res. 2003, 162: 115-32.CrossRef
7.
go back to reference Toi M, Matsumoto T, Bando H: Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol. 2001, 2: 667-73. 10.1016/S1470-2045(01)00556-3.CrossRef Toi M, Matsumoto T, Bando H: Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol. 2001, 2: 667-73. 10.1016/S1470-2045(01)00556-3.CrossRef
8.
go back to reference Poon RT, Fan ST, Wong J: Clinical significance of angiogenesis in gastrointestinal cancers: a target for novel prognostic and therapeutic approaches. Ann Surg. 2003, 238: 9-28. 10.1097/00000658-200307000-00003. Poon RT, Fan ST, Wong J: Clinical significance of angiogenesis in gastrointestinal cancers: a target for novel prognostic and therapeutic approaches. Ann Surg. 2003, 238: 9-28. 10.1097/00000658-200307000-00003.
9.
go back to reference Zafirellis K, Agrogiannis G, Zachaki A, Gravani K, Karameris A, Kombouras C: Prognostic significance of VEGF expression evaluated by quantitative immunohistochemical analysis in colorectal cancer. J Surg Res. 2008, 147: 99-107. 10.1016/j.jss.2007.05.041.CrossRef Zafirellis K, Agrogiannis G, Zachaki A, Gravani K, Karameris A, Kombouras C: Prognostic significance of VEGF expression evaluated by quantitative immunohistochemical analysis in colorectal cancer. J Surg Res. 2008, 147: 99-107. 10.1016/j.jss.2007.05.041.CrossRef
10.
go back to reference Zhao ZR, Zhang ZY, Zhang H, Jiang L, Wang MW, Sun XF: Overexpression of Id-1 protein is a marker in colorectal cancer progression. Oncol Rep. 2008, 19: 419-24. Zhao ZR, Zhang ZY, Zhang H, Jiang L, Wang MW, Sun XF: Overexpression of Id-1 protein is a marker in colorectal cancer progression. Oncol Rep. 2008, 19: 419-24.
11.
go back to reference Lin CQ, Singh J, Murata K, Itahana Y, Parrinello S, Liang SH, Gillett CE, Campisi J, Desprez PY: A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells. Cancer Res. 2000, 60: 1332-40. Lin CQ, Singh J, Murata K, Itahana Y, Parrinello S, Liang SH, Gillett CE, Campisi J, Desprez PY: A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells. Cancer Res. 2000, 60: 1332-40.
12.
go back to reference Kleeff J, Ishiwata T, Friess H, Buchler MW, Israel MA, Korc M: The helix-loop-helix protein Id2 is overexpressed in human pancreatic cancer. Cancer Res. 1998, 58: 3769-72. Kleeff J, Ishiwata T, Friess H, Buchler MW, Israel MA, Korc M: The helix-loop-helix protein Id2 is overexpressed in human pancreatic cancer. Cancer Res. 1998, 58: 3769-72.
13.
go back to reference Ouyang XS, Wang X, Lee DT, Tsao SW, Wong YC: Over expression of ID-1 in prostate cancer. J Urol. 2002, 167: 2598-602. 10.1016/S0022-5347(05)65044-6.CrossRef Ouyang XS, Wang X, Lee DT, Tsao SW, Wong YC: Over expression of ID-1 in prostate cancer. J Urol. 2002, 167: 2598-602. 10.1016/S0022-5347(05)65044-6.CrossRef
14.
go back to reference Schindl M, Oberhuber G, Obermair A, Schoppmann SF, Karner B, Birner P: Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer. Cancer Res. 2001, 61: 5703-6. Schindl M, Oberhuber G, Obermair A, Schoppmann SF, Karner B, Birner P: Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer. Cancer Res. 2001, 61: 5703-6.
15.
go back to reference Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G: Overexpression of hypoxia-inducible factor 1α is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 2000, 60: 4693-6. Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G: Overexpression of hypoxia-inducible factor 1α is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 2000, 60: 4693-6.
16.
go back to reference Fong S, Itahana Y, Sumida T, Singh J, Coppe JP, Liu Y, Richards PC, Bennington JL, Lee NM, Debs RJ, Desprez PY: Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis. Proc Natl Acad Sci USA. 2003, 100: 13543-8. 10.1073/pnas.2230238100.CrossRef Fong S, Itahana Y, Sumida T, Singh J, Coppe JP, Liu Y, Richards PC, Bennington JL, Lee NM, Debs RJ, Desprez PY: Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis. Proc Natl Acad Sci USA. 2003, 100: 13543-8. 10.1073/pnas.2230238100.CrossRef
17.
go back to reference Kadesch T: Consequences of heteromeric interactions among helix-loop-helix proteins. Cell Growth Differ. 1993, 4: 49-55. Kadesch T: Consequences of heteromeric interactions among helix-loop-helix proteins. Cell Growth Differ. 1993, 4: 49-55.
18.
go back to reference Kreider BL, Benezra R, Rovera G, Kadesch T: Inhibition of myeloid differentiation by the helix-loop-helix protein Id. Science. 1992, 255: 1700-2. 10.1126/science.1372755.CrossRef Kreider BL, Benezra R, Rovera G, Kadesch T: Inhibition of myeloid differentiation by the helix-loop-helix protein Id. Science. 1992, 255: 1700-2. 10.1126/science.1372755.CrossRef
19.
go back to reference Zhang X, Ling MT, Feng H, Wong YC, Tsao SW, Wang X: Id-I stimulates cell proliferation through activation of EGFR in ovarian cancer cells. Br J Cancer. 2004, 91 (12): 2042-2047. Zhang X, Ling MT, Feng H, Wong YC, Tsao SW, Wang X: Id-I stimulates cell proliferation through activation of EGFR in ovarian cancer cells. Br J Cancer. 2004, 91 (12): 2042-2047.
20.
go back to reference Lee TK, Poon RT, Yuen AP, Ling MT, Wang XH, Wong YC, Guan XY, Man K, Tang ZY, Fan ST: Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1alpha-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma. Clin Cancer Res. 2006, 12: 6910-9. 10.1158/1078-0432.CCR-06-0489.CrossRef Lee TK, Poon RT, Yuen AP, Ling MT, Wang XH, Wong YC, Guan XY, Man K, Tang ZY, Fan ST: Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1alpha-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma. Clin Cancer Res. 2006, 12: 6910-9. 10.1158/1078-0432.CCR-06-0489.CrossRef
21.
go back to reference Ouyang XS, Wang X, Ling MT, Wong HL, Tsao SW, Wong YC: Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway. Carcinogenesis. 2002, 23: 721-5. 10.1093/carcin/23.5.721.CrossRef Ouyang XS, Wang X, Ling MT, Wong HL, Tsao SW, Wong YC: Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway. Carcinogenesis. 2002, 23: 721-5. 10.1093/carcin/23.5.721.CrossRef
22.
go back to reference Takai N, Miyazaki T, Fujisawa K, Nasu K, Miyakawa I: Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma. Cancer Lett. 2001, 165: 185-93. 10.1016/S0304-3835(01)00433-5.CrossRef Takai N, Miyazaki T, Fujisawa K, Nasu K, Miyakawa I: Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma. Cancer Lett. 2001, 165: 185-93. 10.1016/S0304-3835(01)00433-5.CrossRef
23.
go back to reference Damdinsuren B, Nagano H, Kondo M, Yamamoto H, Hiraoka N, Yamamoto T, Marubashi S, Miyamoto A, Umeshita K, Dono K, Nakamori S, Wakasa K, Sakon M, Monden M: Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Int J Oncol. 2005, 26: 319-27. Damdinsuren B, Nagano H, Kondo M, Yamamoto H, Hiraoka N, Yamamoto T, Marubashi S, Miyamoto A, Umeshita K, Dono K, Nakamori S, Wakasa K, Sakon M, Monden M: Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Int J Oncol. 2005, 26: 319-27.
24.
go back to reference Ling MT, Wang X, Lee DT, Tam PC, Tsao SW, Wong YC: Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R). Carcinogenesis. 2004, 25: 517-25. 10.1093/carcin/bgh047.CrossRef Ling MT, Wang X, Lee DT, Tam PC, Tsao SW, Wong YC: Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R). Carcinogenesis. 2004, 25: 517-25. 10.1093/carcin/bgh047.CrossRef
25.
go back to reference Matsuda Y, Yamagiwa S, Takamura M, Honda Y, Ishimoto Y, Ichida T, Aoyagi Y: Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16. Cancer. 2005, 5: 1037-44. 10.1002/cncr.21259.CrossRef Matsuda Y, Yamagiwa S, Takamura M, Honda Y, Ishimoto Y, Ichida T, Aoyagi Y: Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16. Cancer. 2005, 5: 1037-44. 10.1002/cncr.21259.CrossRef
26.
go back to reference Alani RM, Hasskarl J, Grace M, Hernandez MC, Israel MA, Munger K: Immortalization of primary human keratinocytes by the helix-loop-helix protein, Id-1. Proc Natl Acad Sci USA. 1999, 96: 9637-41. 10.1073/pnas.96.17.9637.CrossRef Alani RM, Hasskarl J, Grace M, Hernandez MC, Israel MA, Munger K: Immortalization of primary human keratinocytes by the helix-loop-helix protein, Id-1. Proc Natl Acad Sci USA. 1999, 96: 9637-41. 10.1073/pnas.96.17.9637.CrossRef
27.
go back to reference Yuen HF, Chua CW, Chan YP, Wong YC, Wang X, Chan KW: Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases. Mod Pathol. 2006, 19: 931-41. 10.1038/modpathol.3800602.CrossRef Yuen HF, Chua CW, Chan YP, Wong YC, Wang X, Chan KW: Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases. Mod Pathol. 2006, 19: 931-41. 10.1038/modpathol.3800602.CrossRef
28.
go back to reference Li X, Zhang Z, Xin D, Chua CW, Wong YC, Leung SC, Na Y, Wang X: Prognostic significance of Id-1 and its association with EGFR in renal cell cancer. Histopathology. 2007, 50: 484-90. 10.1111/j.1365-2559.2007.02637.x.CrossRef Li X, Zhang Z, Xin D, Chua CW, Wong YC, Leung SC, Na Y, Wang X: Prognostic significance of Id-1 and its association with EGFR in renal cell cancer. Histopathology. 2007, 50: 484-90. 10.1111/j.1365-2559.2007.02637.x.CrossRef
29.
go back to reference Ding Y, Wang G, Ling MT, Wong YC, Li X, Na Y, Zhang X, Chua CW, Wang X, Xin D: Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion. Int J Oncol. 2006, 28: 847-54. Ding Y, Wang G, Ling MT, Wong YC, Li X, Na Y, Zhang X, Chua CW, Wang X, Xin D: Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion. Int J Oncol. 2006, 28: 847-54.
30.
go back to reference Ling MT, Lau TC, Zhou C, Chua CW, Kwok WK, Wang Q, Wang X, Wong YC: Overexpression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF). Carcinogenesis. 2005, 26: 1668-76. 10.1093/carcin/bgi128.CrossRef Ling MT, Lau TC, Zhou C, Chua CW, Kwok WK, Wang Q, Wang X, Wong YC: Overexpression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF). Carcinogenesis. 2005, 26: 1668-76. 10.1093/carcin/bgi128.CrossRef
31.
go back to reference Wilson JW, Deed RW, Inoue T, Balzi M, Becciolini A, Faraoni P, Potten CS, Norton JD: Expression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index. Cancer Res. 2001, 61: 8803-10. Wilson JW, Deed RW, Inoue T, Balzi M, Becciolini A, Faraoni P, Potten CS, Norton JD: Expression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index. Cancer Res. 2001, 61: 8803-10.
32.
go back to reference Ramírez BS, Alpízar YA, Fernández DR, Hidalgo GG, Capote AR, Rodríguez RP, Fernández LE: Anti-EGFR activation, anti-proliferative and pro-apoptotic effects of polyclonal antibodies induced by EGFR-based cancer vaccine. Vaccine. 2008, 26: 4918-26. 10.1016/j.vaccine.2008.07.018.CrossRef Ramírez BS, Alpízar YA, Fernández DR, Hidalgo GG, Capote AR, Rodríguez RP, Fernández LE: Anti-EGFR activation, anti-proliferative and pro-apoptotic effects of polyclonal antibodies induced by EGFR-based cancer vaccine. Vaccine. 2008, 26: 4918-26. 10.1016/j.vaccine.2008.07.018.CrossRef
33.
go back to reference Levina V, Su Y, Nolen B, Liu X, Gordin Y, Lee M, Lokshin A, Gorelik E: Chemotherapeutic drugs and human tumor cells cytokine network. Int J Cancer. 2008, 123: 2031-40. 10.1002/ijc.23732.CrossRef Levina V, Su Y, Nolen B, Liu X, Gordin Y, Lee M, Lokshin A, Gorelik E: Chemotherapeutic drugs and human tumor cells cytokine network. Int J Cancer. 2008, 123: 2031-40. 10.1002/ijc.23732.CrossRef
34.
go back to reference Tortora G, Ciardiello F, Gasparini G: Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nat Clin Pract Oncol. 2008, 5: 521-30. 10.1038/ncponc1161.CrossRef Tortora G, Ciardiello F, Gasparini G: Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nat Clin Pract Oncol. 2008, 5: 521-30. 10.1038/ncponc1161.CrossRef
35.
go back to reference Galizia G, Lieto E, Ferraraccio F, De Vita F, Castellano P, Orditura M, Imperatore V, La Mura A, La Manna G, Pinto M, Catalano G, Pignatelli C, Ciardiello F: Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery. Ann Surg Oncol. 2006, 13: 823-35. 10.1245/ASO.2006.05.052.CrossRef Galizia G, Lieto E, Ferraraccio F, De Vita F, Castellano P, Orditura M, Imperatore V, La Mura A, La Manna G, Pinto M, Catalano G, Pignatelli C, Ciardiello F: Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery. Ann Surg Oncol. 2006, 13: 823-35. 10.1245/ASO.2006.05.052.CrossRef
36.
go back to reference Kim HJ, Chung H, Yoo YG, Kim H, Lee JY, Lee MO, Kong G: Inhibitor of DNA binding 1 activates vascular endothelial growth factor through enhancing the stability and activity of hypoxia-inducible factor-1alpha. Mol Cancer Res. 2007, 5: 321-9. 10.1158/1541-7786.MCR-06-0218.CrossRef Kim HJ, Chung H, Yoo YG, Kim H, Lee JY, Lee MO, Kong G: Inhibitor of DNA binding 1 activates vascular endothelial growth factor through enhancing the stability and activity of hypoxia-inducible factor-1alpha. Mol Cancer Res. 2007, 5: 321-9. 10.1158/1541-7786.MCR-06-0218.CrossRef
Metadata
Title
Id-1: Regulator of EGFR and VEGF and potential target for colorectal cancer therapy
Authors
Ibrahim Meteoglu
Nezih Meydan
Muhan Erkus
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2008
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-27-69

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