Modulation of the expression of the Cip/Kip family of cyclin-dependent kinase inhibitors in foetal developing lungs of hamsters.
We examine the cell proliferation activity and expression of cyclin-dependent kinase inhibitors of the Cip/Kip family, p21Cip1, p27Kip1 and p57Kip2, in foetal hamster lungs to determine the expression patterns of the cyclin-dependent kinase inhibitors and to clarify the relationship between expression of the cyclin-dependent kinase inhibitors and lung development. Foetal hamster lungs on gestational days 12.5-16 (the day of birth) and adult lungs were fixed in 4% paraformaldehyde. Frozen sections were immunostained for the cyclin-dependent kinase inhibitors, and examined by immunostaining for Ki-67 and bromodeoxyuridine to determine the proliferation activity of the foetal lungs. During the foetal period, cell proliferation activity, as analysed by Ki-67 or bromodeoxyuridine labelling, decreased with development of the lung. In contrast to the gradual decrease of cell proliferation activity, cells with p27Kip1 immunoreactivity increased with development. On the other hand, p21Cip1-positive cells were most prominent around gestational day 14.5, while after birth positive cells decreased markedly. A few p57Kip2-positive cells were detected in the bronchiolar epithelium on gestational day 14.5. Western blotting analyses confirmed these immunostaining patterns. Thus, the levels of the cyclin-dependent kinase inhibitors of the Cip/Kip family are modulated in the lungs during the foetal period, and each shows a unique expression pattern. The cyclin-dependent kinase inhibitors may play roles not only in regulating cell proliferation activity but also in regulating other functions such as differentiation in the lung during the foetal period.
Ikoma
T
T
Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan.
Ito
T
T
Okudela
K
K
Hayashi
H
H
Yazawa
T
T
Kitamura
H
H
D000375:Aging / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D006224:Cricetinae; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D009687:Nuclear Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine