EXPRESSION OF THE CYCLIN-DEPENDENT KINASE CDK4 IN PERINATAL AND ADULT-RAT LUNG

The identification of numerous cyclin-dependent kinases (cdk) and G1 cyclins suggests that cell cycle progression through G1/S may be controlled in a tissue-specific manner by various cdk/cyclin complexes. In situ hybridization was used to characterize expression of the cyclin-dependent kinase cdk4 in prenatal and postnatal rat lung and other tissues and to determine whether cdk4 expression is limited to proliferating cells, identified by BrdU incorporation and cdk1 mRNA expression. cdk4 co-localized with cdk1 in proliferating cells of both prenatal and postnatal lung and other tissues, consistent with an SPF function that is not tissue-specific. The distribution of cdk1 and cdk4 expression was identical in fetal rat tissues and was detected in lung parenchyma and throughout the airway. Pulmonary cell proliferation declined with increasing postnatal age and could be found only in focal areas of day 21 terminal and respiratory bronchiolar epithelium. Proliferation was undetectable in adult lung. Postnatal cdk4 expression was not restricted to cells expressing cdk1: cdk4 was evenly distributed in bronchiolar epithelium and was present throughout the airway and alveolar septae of day 21 lung. Expression of cdk4 was also maintained in adult bronchiolar epithelium. These studies demonstrate that although the expression of cdk1 is tightly correlated with proliferative capacity, the expression of cdk4 is not limited to proliferating cells, suggesting that cdk4 may have additional cell-specific functions unrelated to cell cycle progression.