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-depende nt kinase inhibitors of the Cip/Kip family, p21Cip1, p27Kip1 and p57Kip2, i n foetal hamster lungs to determine the expression patterns of the cyclin-d ependent kinase inhibitors and to clarify the relationship between expressi on of the cyclin-dependent kinase inhibitors and lung development. Foetal h amster 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 deter-mine the proliferation activity of the foetal lungs. During the foetal period, cell proliferation activity, as an alysed by Ki-67 or bromodeoxyuridine labelling, decreased with development of the lung. In contrast to the gradual decrease of cell proliferation acti vity, cells with p27Kip1 immunoreactivity increased with development. On th e other hand, p21Cip1-positive cells were most prominent around gestational day 14.5, while after bir-th positive cells decreased markedly. A few p57K ip2-positive cells were detected in the bronchiolar epithelium on gestation al day 14.5. Western blotting analyses confirmed these immunostaining patte rns. 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 sh ows 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 f oetal period.