Differential expression of cyclin D2 and cdc2 genes in proliferating and nonproliferating alveolar epithelial cells.
Alveolar epithelial cells (AEC) proliferate during embryonic and fetal life, while in the adult lung AEC form a highly differentiated population that does not usually divide. Herein, we tested the hypothesis that differential expression of specific cell cycle control genes may occur during AEC development and transformation. We compared normal rat AEC in primary culture with transformed AEC for the expression of D-type G1 cyclins and cyclin-dependent protein kinases (cdc2 and cdk2). Cyclin D1 mRNA and protein were expressed at comparable levels in both normal rat AEC and in transformed AEC. In contrast, high levels of cyclin D2 mRNA and protein expression were only observed in normal 19-day fetal rat AEC and in transformed mink Mv1Lu cells derived from fetal mink lung epithelium. Moreover, treatment either with antisense oligodeoxynucleotides directed against cyclin D2 mRNA or with genistein (a tyrosine kinase inhibitor) caused significant inhibition of [3H]thymidine incorporation into DNA as well as inhibition of cyclin D2 expression in normal 19-day fetal rat AEC. p34cdc2 (but not p33cdk2 or p34cdk4) was expressed at progressively decreasing levels with corresponding histone H1 kinase activities during rat AEC development (19-day fetal > 21-day fetal > 13-day postnatal > adult rat AEC). The levels of p34cdc2 histone H1 kinase activity were significantly up-regulated or amplified in adult rat type 2 AEC following hyperoxic injury and repair and in transformed AEC. Collectively, these data support an important functional role for cyclin D2 and cdc2 genes in determining the proliferative versus nonproliferative phenotype of AEC during lung development, injury and repair, and transformation.
Wu
F
F
Department of Pediatrics, Childrens Hospital of Los Angeles, University of Southern California School of Medicine 90027.
Buckley
S
S
Bui
K C
KC
Warburton
D
D
D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells; D018507:Gene Expression Regulation, Developmental; D018816:Genes, cdc / Q000235:genetics* / Q000502:physiology; D018496:Hyperoxia; D008969:Molecular Sequence Data; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
C486197:Ccnd2 protein, rat; D056742:Cyclin D2; D016213:Cyclins; D012333:RNA, Messenger; D004247:DNA; D016203:CDC2 Protein Kinase