Differential Distribution and Increased Levels of Ras Proteins During Lung Development

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Abstract
Differential localization of ras proteins and variations in their levels may be of importance during lung growth and differentiation. Abundant cell proliferation occurs during development of the fetal rat lung. As assessed by flow cytometry the proliferative activity declined near birth, followed by a gradual increase in cellular proliferation during the subsequent 8 days and a decline to basal levels by 15 to 18 days of age. During this period of substantial variations in proliferative activity, differences in both the protein content and localization of the different ras proteins were observed. The content of N- and K-ras proteins in lung homogenates increased 5 to 6-fold in rats 20 days or older, compared to fetal levels. The protein levels of the ras proteins remained elevated when cellular proliferation decreased to basal 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 increased in abundance during postnatal development.