PT - JOURNAL ARTICLE AU - Tsujiuchi, Toshifumi AU - Tsutsumi, Masahiro AU - Sasaki, Yasutaka AU - Murata, Nao AU - Konishi, Yoichi TI - Mutations of <em>Adenomatous Polyposis Coli</em> and <em>β</em><em>-Catenin</em> Genes during Progression of Lung Tumors Induced by <em>N</em>-Nitrosobis(2-hydroxypropyl)amine in Rats DP - 2000 Dec 01 TA - Cancer Research PG - 6611--6616 VI - 60 IP - 23 4099 - http://cancerres.aacrjournals.org/content/60/23/6611.short 4100 - http://cancerres.aacrjournals.org/content/60/23/6611.full SO - Cancer Res2000 Dec 01; 60 AB - In the present study, we investigated mutations of the adenomatous polyposis coli (APC) and β-catenin genes to clarify possible molecular mechanisms underlying development of lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 weeks of age, were given 2000 ppm BHP in drinking water for 12 weeks and then maintained without further treatment until sacrifice at week 25. DNA was extracted from paraffin-embedded tissues, and PCR-single-strand conformation polymorphism analysis, followed by nucleotide sequencing, was performed. No APC mutations were detected in 17 hyperplasias, but 2 of 15 adenomas (13.3%) and 8 of 20 adenocarcinomas (40.0%) showed changes within exon 1 to the mutation cluster region in exon 15. For β-catenin, no mutations were detected in 17 hyperplasias, but 3 of 15 adenomas (20.0%) and 5 of 20 adenocarcinomas (25.0%) had alterations within or flanking codons corresponding to important phosphorylation sites. Immunohistochemical staining showed β-catenin protein localized in the cell membranes in the surrounding normal-appearing lung and 216 hyperplasias and localized mainly in the cytoplasm and/or nucleus in 10 of 37 adenomas (27.0%) and 21 of 40 adenocarcinomas (52.5%). These results suggest that the APC-β-catenin-T-cell factor signaling pathway is involved in the acquisition of growth advantage from adenomas to adenocarcinomas in BHP-induced rat lung carcinogenesis. ©2000 American Association for Cancer Research.