CYCLIN-DEPENDENT KINASE INHIBITOR EXPRESSION IN PULMONARY CLARA CELLSTRANSFORMED WITH SV40 LARGE T-ANTIGEN IN TRANSGENIC MICE

Expression of cell cycle regulatory genes in mouse lung was investigat ed in transgenic models for Clara cell transformation, Clara cells wer e transformed by generating transgenic mice in which the SV40 large T antigen was expressed under the control of the mouse Clara cell M(r) 1 0,000 protein promoter. The resulting lung tumors express the large T antigen in normal Clara cells and in tumors, and these tumors express reduced levels of CC10 mRNA. The expression of cell cycle regulatory p rotein, p53, and the cyclin-dependent kinase inhibitors was analyzed b y Northern blot analysis and in situ hybridization throughout the prog ression of Clara cell transformation in the lung, Increases in specifi c cyclin-dependent kinase inhibitor steady-state mRNA levels were dete cted in p15, p18, p27, and p57 during tumor progression, The expressio n of p15, p57, and p21 mRNAs were verified by in situ hybridization, U sing this approach, regulatory genes have been identified that may be involved in the regulation of Clara cell differentiation.