Overexpression of midkine in lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine in rats and its increase with progression

The expression of midkine (MK) in lung tumors induced by N-nitrosobis(2-hyd roxypropyl)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 wi thout 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 em bryonic tissues (positive controls) and contrasted strongly with the lack i n normal lungs. MK protein was detected immunohistochemically in 58.3% of a lveolar hyperplasias, 92.3% of adenomas and 100% of adenocarcinomas and squ amous cell carcinomas. The extent of staining significantly increased along with malignant progression in adenomatous (pre-)neoplastic lesions and ten ded to become more pronounced with malignant progression in squamous lesion s. The results suggest that MK may play some essential roles in the develop ment and progression of lung tumors induced by BHP in rats.