Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma.
Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma.
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DOI：
10.1186/1471-2407-13-509
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发表时间：
2013-10-30
期刊：
影响因子：
3.8
通讯作者：
Kamai T
中科院分区：
文献类型：
--
作者：
Betsunoh H;Fukuda T;Anzai N;Nishihara D;Mizuno T;Yuki H;Masuda A;Yamaguchi Y;Abe H;Yashi M;Fukabori Y;Yoshida K;Kamai T
L系统氨基酸转运蛋白（LAT）在多种氨基酸的转运中具有重要作用，并且已有关于该系统与癌症关系的报道。尽管 LAT 在肾脏中高度表达，但其对人类肾癌的影响却知之甚少。为了阐明 LAT 在人透明细胞肾细胞癌 (RCC) 中的作用，我们研究了透明细胞 RCC 组织中 LAT1、LAT2、LAT3、LAT4 和 4F2hc 的 mRNA 表达。通过实时逆转录聚合酶链式反应，对 82 名日本透明细胞肾细胞癌患者手术时获得的匹配组肿瘤和非肿瘤组织中的这 5 个基因的 mRNA 进行了分析。我们还通过蛋白质印迹法测量了患者 18 对肿瘤和非肿瘤组织中的磷酸化 S6 核糖体蛋白 (Ser-235/236) 蛋白水平。与非肿瘤组织相比，肿瘤组织中LAT1 mRNA的表达显着升高，而LAT2和LAT3 mRNA的表达降低。肿瘤组织和非肿瘤组织中LAT4和4F2hc mRNA的表达没有差异。 LAT1 mRNA 表达增加与低分化肿瘤、局部侵袭、显微血管侵袭和转移相关。 Kaplan-Meier 生存分析表明，较高的血清 LAT1 mRNA 水平与较短的总生存时间相关。磷酸化 S6 核糖体蛋白水平与转移潜力相关。原发性肿瘤中 LAT1 mRNA 水平与磷酸化 S6 核糖体蛋白水平呈正相关。这些发现表明 LAT1 mRNA 与透明细胞肾细胞癌的侵袭和进展潜力相关。
The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer. To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting. Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors. These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.
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影响因子：
11.2
作者：
Dang CV
通讯作者：
Dang CV
影响因子：
8.8
作者：
Kaira, K.;Oriuchi, N.;Imai, H.;Shimizu, K.;Yanagitani, N.;Sunaga, N.;Hisada, T.;Tanaka, S.;Ishizuka, T.;Kanai, Y.;Endou, H.;Nakajima, T.;Mori, M.
通讯作者：
Mori, M.
DOI：
10.1007/s00262-011-0989-3
发表时间：
2011-06
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Furuya N;Kamai T;Shirataki H;Yanai Y;Fukuda T;Mizuno T;Nakamura F;Kambara T;Nakanishi K;Abe H;Yoshida K
通讯作者：
Yoshida K
影响因子：
5.3
作者：
Kim, JW;Zeller, KI;Dang, CV
通讯作者：
Dang, CV
DOI：
10.1158/1078-0432.ccr-09-0889
发表时间：
2009-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dang CV;Le A;Gao P
通讯作者：
Gao P