LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung
LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung
复制标题
DOI：
10.1007/s00428-005-0063-7
复制
发表时间：
2006-02-01
期刊：
影响因子：
3.5
通讯作者：
Kawai, T
中科院分区：
文献类型：
--
作者：
Nakanishi, K;Matsuo, H;Kawai, T
之前没有研究调查过中性大氨基酸转运蛋白1型（LAT1）在正常肺细胞、非典型腺瘤性增生（AAH）和肺非粘液细支气管肺泡癌（NMBAC）中的作用。(1)采用半定量逆转录-聚合酶链反应检测41例正常肺组织和34例NMBAC组织中LAT1 mRNA/ GAPDH mRNA水平；(2)原位杂交和免疫组化检测35例正常肺组织、34例AAH（11例为低级别AAH， 23例为高级别AAH）和43例NMBAC组织中LAT1 mRNA和蛋白的表达；(2)这些病变中LAT1 mRNA和蛋白表达的发生率与细胞增殖的关系。NMBAC的LAT1 mRNA/GAPDH mRNA水平(1)倾向于高于正常肺组织（12.0 +/- 8.1），高于正常肺组织（1.0 +/- 0.2）；(2)NMBAC的范围（0 - 276）远高于正常肺组织（0 - 5.8），有6个NMBAC的值高于7.0，而正常肺组织中检测到的最高值为5.8。在周围正常肺组织中，支气管表面上皮细胞和肺泡巨噬细胞中检测到LAT1 mRNA和蛋白（但在非纤毛细支气管上皮细胞和肺泡I型和II型细胞中未检测到）。在支气管表面上皮细胞中，LAT1蛋白呈结节型，被认为是一种无功能的蛋白模式。低级别AAH中LAT1 mRNA和蛋白的阳性表达率分别为54.5%和27.3%，高级别AAH中为65.2和52.2%，NMBAC中为65.1和79.1%。在LAT1蛋白表达的情况下，总的（低级别加高级别）AAH与NMBAC、低级别AAH与NMBAC之间存在显著差异。因此，就LAT1蛋白表达的发生率而言，高级别AAH出现在低级别AAH和NMBAC之间。lta1蛋白阳性的AAH和NMBAC的Ki-67标记指数（细胞增殖评分）明显高于lat1蛋白阴性的AAH和NMBAC。综上所述，在高级别AAH和NMBAC中，LAT1的表达可能随着代谢活性和细胞增殖的上调而增加。
No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription-polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0 +/- 8.1) than in normal lung tissues (1.0 +/- 0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.