Sakitani H, Tsutsumi M, Kadomatsu K, Ikematsu S, Takahama M, Iki K, Tsujiuchi T, Muramatsu T, Sakuma S, Sakaki T, Konishi Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Carcinogenesis. 1999 Mar;20(3):465-9. doi: 10.1093/carcin/20.3.465.
The expression of midkine (MK) in lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats was examined. The animals were administered 2000 p.p.m. of BHP in their drinking water for 12 weeks, then maintained without further treatment until being killed 20-28 weeks after the beginning of the experiment. MK mRNA expression of adenocarcinomas and squamous cell carcinomas assessed by means of the reverse transcriptase-polymerase chain reaction and northern blot analysis was significantly higher than in rat embryonic tissues (positive controls) and contrasted strongly with the lack in normal lungs. MK protein was detected immunohistochemically in 58.3% of alveolar hyperplasias, 92.3% of adenomas and 100% of adenocarcinomas and squamous cell carcinomas. The extent of staining significantly increased along with malignant progression in adenomatous (pre-)neoplastic lesions and tended to become more pronounced with malignant progression in squamous lesions. The results suggest that MK may play some essential roles in the development and progression of lung tumors induced by BHP in rats.
检测了N-亚硝基双（2-羟丙基）胺（BHP）诱导的大鼠肺肿瘤中中期因子（MK）的表达。给动物饮用含2000 ppm BHP的水12周，然后不再进行进一步处理，直至在实验开始后20 - 28周处死。通过逆转录聚合酶链反应和Northern印迹分析评估，腺癌和鳞状细胞癌中MK mRNA的表达显著高于大鼠胚胎组织（阳性对照），与正常肺组织中缺乏MK形成强烈对比。免疫组织化学检测发现，58.3%的肺泡增生、92.3%的腺瘤以及100%的腺癌和鳞状细胞癌中可检测到MK蛋白。在腺瘤性（癌前）病变中，染色程度随恶性进展显著增加，在鳞状病变中也随恶性进展而趋于更明显。结果表明，MK可能在BHP诱导的大鼠肺肿瘤发生和进展中发挥某些重要作用。
