DIFFERENTIAL DISTRIBUTION AND INCREASED LEVELS OF RAS PROTEINS DURINGLUNG DEVELOPMENT

Differential localization of ras proteins and variations in their leve ls may be of importance during lung growth and differentiation. Abunda nt cell proliferation occurs during development of the fetal rat lung. As assessed by flow cytometry the proliferative activity declined nea r birth, followed by a gradual increase in cellular proliferation duri ng the subsequent 8 days and a decline to basal levels by 15 to 18 day s of age. During this period of substantial variations in proliferativ e activity, differences in both the protein content and localization o f the different ras proteins were observed. The content of N- and K-ra s proteins in lung homogenates increased 5- to 6-fold in rats 20 days or alder, compared to fetal levels. The protein levels of the ras prot eins remained elevated when cellular proliferation n decreased to basa l levels. As determined by immunohistochemistry, the localization of N -ras protein was restricted to keratin expressing cells of bronchiolar structures, apparently mainly ciliated cells. In contrast, K-ras was found in alveolar cells, probably type I and type 2 cells. H-ras, but not K- or N-ras, was localized to nonepithelial cells. Thus, different ras proteins were localized to different regions of the lung and incr eased in abundance during postnatal development.