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摘要: 目的:分析表皮生长因子受体家族中的ErbB-3受体和氨基酸转运蛋白L型氨基酸转运体-1(LAT-1)在临床前列腺癌组织标本中的表达和定位,以及二者之间可能存在的相关性。方法:对45例前列腺癌组织标本,10例良性前列腺增生组织(BPH)标本和9例正常前列腺标本的石蜡切片采用免疫组织化学SABC方法染色并进行分析。结果:在45例前列腺癌组织中有33例(73.3%)细胞质或细胞核呈现ErbB-3染色阳性;10例BPH标本中,仅有1例出现阳性反应(P<0.001);正常前列腺组织中未见到阳性表达(P<0.001)。而LAT-1在前列腺癌组织中的表达阳性率高于ErbB-3,为40例(88.9%),表达于细胞膜和或细胞质中,明显高于正常组织以及BPH组织(P<0.05)。LAT-1在正常组织和BPH组织中无阳性表达。ErbB-3和LAT-1在前列腺癌组织中的表达均与Glean评分分级无关。在前列腺癌组织中ErbB-3和LAT-1的表达存在正相关性(r=0.426,P<0.05)。结论:在前列腺组织中的ErbB-3和LAT-1阳性表达和定位能够区分恶性肿瘤与BPH和正常前列腺组织,有利于前列腺癌的诊断和生物学的预测。
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关键词:
- 前列腺癌 /
- 良性前列腺增生 /
- ErbB-3受体 /
- 氨基酸转运蛋白LAT-1
Abstract: Objective:The ErbB1and ErbB2 receptors have been implicated in prostate cancer progression, but less is known about the role and biology of new receptor family members in prostate cancer. While, heterodimeric large amino acid transporter (L-type amino acid transporter) that are expressed in various tissues including most solid tumors is responsible for supporting tumors energy. But less available information about LAT-1 in reports in prostate cancer. The aim of this study was to analyze the expression and localization of ErbB-3 and LAT-1 in prostate tissues and the correlation of their expression.Method:Immunohistochemistry of and LAT-1 was done on prostate cancer tissue sections from 45 patients and 10 benign prostatic hyperplasia patients and 9 nomal people.Result:Immunohistochemistry analysis of prostate cancer tissues revealed that 73.3% and 88.9%, prostate cancer tissues displayed or nuclear ErbB-3 staining and cytoplasmic or cytoplasmic membrane LAT-1 staining, respectively. Minimal ErbB-3 nuclear staining was observed in normal prostate tissues and benign prostatic hyperplasia tissues. Additionally, increased nuclear ErbB-3 and LAT-1 were not associated with increasing Gleason grade. There was significant correlation between the expression of ErbB-3 and LAT-1 in prostate cancer.Conclusion:ErbB-3 and LAT-1 cytoplasmic and(or) nuclear localization discriminates normal and benign prostatic hyperplasia from malignant prostate tissues. They will be useful in predicting tumor biological behavior and may help for diagnosing and clinical decision-making in the treatment of prostate cancer patients.-
Key words:
- prostate cancer /
- BPH /
- ErbB-3 receptor /
- LAT-1
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[1] HYNES N E,LANE H A.ERBB receptors andcancer:the complexity of targeted inhibitors[J].NatRev Cancer,2005,5:341-354.
[2] 许良中,杨文涛.免疫组织化学反应结果的判断标准.中国癌症杂志,1996,6(4):229-231.
[3] KOUMAKPAYI I H,DIALLO J S,LE PAGE C,etal.Expression and nuclear localization of ErbB3inprostate cancer[J].Clin Cancer Res,2006,12:2730-2737.
[4] SAKATA T,FERDOUS G,TSURUTA T,et al.L-type amino-acid transporter 1as a novel biomarkerfor high-grade malignancy in prostate cancer[J].Pathol Int,2009,59:7-18.
[5] HOLBRO T,CIVENNI G,HYNES N E.The ErbBreceptors and their role in cancer progression[J].Exp Cell Res,2003,284:99-110.
[6] YARDEN Y.The EGFR family and its ligands in hu-man cancer.Signalling mechanisms and therapeuticopportunities[J].Eur J Cancer,2001,37Suppl 4:S3-S8.
[7] LEE-HOEFLICH S T,CROCKER L,YAO E,etal.A central role for HER3in HER2-amplifiedbreast cancer:implications for targeted therapy[J].Cancer Res,2008,68:5878-5887.
[8] GREGORY C W,WHANG Y E,MCCALL W,etal.Heregulin-induced activation of HER2and HER3increases androgen receptor transactivation andCWR-R1 human recurrent prostate cancer cellgrowth[J].Clin Cancer Res,2005,11:1704-1712.
[9] EDWARDS J,TRAYNOR P,MUNRO A F,et al.The role of HER1-HER4and EGFRvIII in hormone-refractory prostate cancer[J].Clin Cancer Res,2006,12:123-130.
[10] WAGNER C A,LANG F,BRER S.Function andstructure of heterodimeric amino acid transporters[J].Am J Physiol Cell Physiol,2001,281:C1077-1093.
[11] BODOY S,MARTN L,ZORZANO A,et al.Iden-tification of LAT4,a novel amino acid transporterwith system L activity[J].J Biol Chem,2005,280:12002-12011.
[12] FUCHS B C,BODE B P.Amino acid transportersASCT2and LAT1in cancer:partners in crime[J]?Semin Cancer Biol,2005,15:254-266.
[13] KANAI Y,ENDOU H.Heterodimeric amino acidtransporters:molecular biology and pathological andpharmacological relevance[J].Curr Drug Metab,2001,2:339-354.
[14] SOARES-DA-SILVA P,SERRO M P.Apical andbasolateral 4F2hc and the amino acid exchange of L-DOPA in renal LLC-PK1cells[J].Amino Acids,2005,29:213-219.
[15] UCHINO H,KANAI Y,KIM D K,et al.Trans-port of amino acid-related compounds mediated by L-type amino acid transporter 1(LAT1):insights intothe mechanisms of substrate recognition[J].MolPharmacol,2002,61:729-737.
[16] YARDEN Y.The EGFR family and its ligands in hu-man cancer.signalling mechanisms and therapeuticopportunities[J].Eur J Cancer,2001,37Suppl 4:S3-S8.
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