REGULATION OF THE RAT BB1 RNA DURING NORMAL RAT LUNG DEVELOPMENT

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BB1 was recently cloned from the WI-38 human fetal lung cell line. Human BB1 (hBB1) is expressed by multiple tissues, including lung. Because inhibition of BB1 translation using antisense oligodeoxynucleotides resulted in prevention of G1 traversal in cultured cells, we hypothesized that BB1 gene expression would be regulated during lung development with greater expression during periods of active lung growth. To gain insight into the expression of BB1 during lung development, a rat BB1 (rBB1) homologue was cloned and used in Northern hybridization analyses and in situ hybridization histochemistry (ISHH). Northern hybridization analyses of fetal and postnatal rat lung demonstrate that rBB1 RNA abundance is relatively low on fetal days E17 through E19, with a small peak of expression occurring on fetal day E20, then increases at birth with peak expression in adult lung. ISHH correlates with the Northern hybridization data and reveals rBB1 RNA expression throughout lung from E17to E21in both epithelium and mesenchyme. In postnatal lung, more intense expression of BB1 was observed than in fetal lung, localizing BB1 transcripts to proximal and distal airways and mesenchymal cells surrounding airways. Proliferating cell nuclear antigen (PCNA) was identified in lung sections adjacent to those used for ISHH and it was found that BB1 expression was present in PCNA positive cells; however, BB1 expression was not limited to PCNA-positive cells in either the fetal or postnatal periods. This was most apparent in adult (60-day) rat lung where essentially no PCNA positive cells were detected, but intense BB1 expression was detected in airway epithelium and surrounding mesenchyme. These studies demonstrate developmental regulation of BB1 during lung development. The findings are consistent with BB1 action in cell growth-related processes of fetal and early postnatal lung; however, the distribution of BB1 expression in relation to PCNA localization suggests that BB1 participates in cellular functions in addition to cell proliferation.