Abstract: The disruption of cell-matrix interactions influences the expression of a number of cell cycle regulatory proteins such as p21, p27 and p53. In this study, Clara cells obtained form both wildtype (wt) and p21 knockout (p21 ko) mice were isolated and cultured on different ECM combinations and the expression of three cyclin kinase inhibitors p21, p27 and p53 were studied. Distruption of the cell-matrix resulted in a decrease in the expression of cytoplasmic p21 and cytoplasmic p27. Nuclear p53 expression was found to increase in Clara cells lacking p21 and although the variation of ECM combinations did not affect the expression of p53. Although the p27 expression did not significantly changes upon culturing the cells in different compositions of ECM, disruption of the cell-matrix interactions seems to be influential.