期刊论文详细信息
BMC Research Notes
Gene expression pattern of the epidermal growth factor receptor family and LRIG1 in renal cell carcinoma
Roger Henriksson1  Börje Ljungberg2  Håkan Hedman1  Marcus Thomasson1 
[1] Department of Radiation Sciences, Umeå University, SE-901 87, Umeå, Sweden;Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University, SE-901 87, Umeå, Sweden
关键词: Survival;    LRIG1;    ERRB4;    ERBB3;    ERBB2;    EGFR;    Renal cell carcinoma;   
Others  :  1166460
DOI  :  10.1186/1756-0500-5-216
 received in 2012-01-30, accepted in 2012-05-03,  发布年份 2012
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【 摘 要 】

Background

Previous studies have revealed altered expression of epidermal growth factor receptor (EGFR)-family members and their endogenous inhibitor leucine-rich and immunoglobulin-like domains 1 (LRIG1) in renal cell carcinoma (RCC). In this study, we analyzed the gene expression levels of EGFR-family members and LRIG1, and their possible associations with clinical parameters in various types of RCC.

Methods

Gene expression levels of EGFR–family members and LRIG1 were analyzed in 104 RCC samples, including 81 clear cell RCC (ccRCC), 15 papillary RCC (pRCC), and 7 chromophobe RCC (chRCC) by quantitative real-time RT-PCR. Associations between gene expression levels and clinical data, including tumor grade, stage, and patient survival were statistically assessed.

Results

Compared to kidney cortex, EGFR was up-regulated in ccRCC and pRCC, LRIG1 and ERBB2 were down-regulated in ccRCC, and ERBB4 was strongly down-regulated in all RCC types. ERBB3 expression did not differ between RCC types or between RCC and the kidney cortex. The expression of the analyzed genes did not correlate with patient outcome.

Conclusions

This study revealed that the previously described up-regulation of EGFR and down-regulation of ERBB4 occurred in all analyzed RCC types, whereas down-regulation of ERBB2 and LRIG1 was only present in ccRCC. These observations illustrate the need to evaluate the different RCC types individually when analyzing molecules of interest and potential biological markers.

【 授权许可】

   
2012 Thomasson et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Störkel S, Eble J, Adlakha K, Amin M, Blute M, Bostwick D, Darson M, Delahunt B, Iczkowski K: Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 1997, 80:987-989.
  • [2]Linehan WM, Vasselli J, Srinivasan R, Walther MM, Merino M, Choyke P, Vocke C, Schmidt L, Isaacs JS, Glenn G, et al.: Genetic basis of cancer of the kidney: disease-specific approaches to therapy. Clin Cancer Res 2004, 10:6282S-6289S.
  • [3]Baldewijns MM, van Vlodrop IJ, Schouten LJ, Soetekouw PM, de Bruine AP, van Engeland M: Genetics and epigenetics of renal cell cancer. Biochim Biophys Acta 2008, 1785:133-155.
  • [4]Yarden Y, Sliwkowski M: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001, 2:127-137.
  • [5]Olayioye M, Neve R, Lane H, Hynes N: The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000, 19:3159-3167.
  • [6]Nilsson J, Vallbo C, Guo D, Golovleva I, Hallberg B, Henriksson R, Hedman H: Cloning, characterization, and expression of human LIG1. Biochem Biophys Res Commun 2001, 284:1155-1161.
  • [7]Gur G, Rubin C, Katz M, Amit I, Citri A, Nilsson J, Amariglio N, Henriksson R, Rechavi G, Hedman H, et al.: LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. EMBO J 2004, 23:3270-3281.
  • [8]Laederich MB, Funes-Duran M, Yen L, Ingalla E, Wu X, Carraway KL, Sweeney C: The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. J Biol Chem 2004, 279:47050-47056.
  • [9]Goldoni S, Iozzo RA, Kay P, Campbell S, McQuillan A, Agnew C, Zhu JX, Keene DR, Reed CC, Iozzo RV: A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity. Oncogene 2007, 26:368-381.
  • [10]Yi W, Holmlund C, Nilsson J, Inui S, Lei T, Itami S, Henriksson R, Hedman H: Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1. Exp Cell Res 2011, 317:504-512.
  • [11]Shattuck DL, Miller JK, Laederich M, Funes M, Petersen H, Carraway KL, Sweeney C: LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy. Mol Cell Biol 2007, 27:1934-1946.
  • [12]Ledda F, Bieraugel O, Fard SS, Vilar M, Paratcha G: Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF. J Neurosci 2008, 28:39-49.
  • [13]Miller JK, Shattuck DL, Ingalla EQ, Yen L, Borowsky AD, Young LJ, Cardiff RD, Carraway KL, Sweeney C: Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer. Cancer Res 2008, 68:8286-8294.
  • [14]Hedman H, Nilsson J, Guo D, Henriksson R: Is LRIG1 a tumour suppressor gene at chromosome 3p14.3? Acta Oncol 2002, 41:352-354.
  • [15]Tanemura A, Nagasawa T, Inui S, Itami S: LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases. Dermatol Surg 2005, 31:423-430.
  • [16]Lindstrom AK, Ekman K, Stendahl U, Tot T, Henriksson R, Hedman H, Hellberg D: LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking. Int J Gynecol Cancer 2008, 18:312-317.
  • [17]Krig SR, Frietze S, Simion C, Miller JK, Fry WH, Rafidi H, Kotelawala L, Qi L, Griffith OL, Gray JW, et al.: Lrig1 Is an Estrogen-Regulated Growth Suppressor and Correlates with Longer Relapse-Free Survival in ER{alpha}-Positive Breast Cancer. Mol Cancer Res 2011, 9:1406-1417.
  • [18]Thomasson M, Hedman H, Guo D, Ljungberg B, Henriksson R: LRIG1 and epidermal growth factor receptor in renal cell carcinoma: A quantitative RT-PCR and immunohistochemical analysis. Br J Cancer 2003, 89:1285-1289.
  • [19]Thomasson M, Hedman H, Junttila TT, Elenius K, Ljungberg B, Henriksson R: ErbB4 is downregulated in renal cell carcinoma–a quantitative RT-PCR and immunohistochemical analysis of the epidermal growth factor receptor family. Acta Oncol 2004, 43:453-459.
  • [20]Hofmockel G, Riess S, Bassukas I, Dammrich J: Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact. Eur Urol 1997, 31:478-484.
  • [21]Yoshida K, Tosaka A: Epidermal growth factor binding by membranes of human renal cell carcinomas: establishment of an epidermal growth factor receptor assay for clinical use. Int J Urol 1994, 1:319-323.
  • [22]Lager D, Slagel D, Palechek P: The expression of epidermal growth factor receptor and transforming growth factor alpha in renal cell carcinoma. Mod Pathol 1994, 7:544-548.
  • [23]Ljungberg B, Gafvels M, Damber J: Epidermal growth factor receptor gene expression and binding capacity in renal cell carcinoma, in relation to tumor stage, grade and DNA ploidy. Urol Res 1994, 22:305-308.
  • [24]Sakaeda T, Okamura N, Gotoh A, Shirakawa T, Terao S, Morioka M, Tokui K, Tanaka H, Nakamura T, Yagi M, et al.: EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients. Pharm Res 2005, 22:1757-1761.
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