Regulation of the rat BB1 RNA during normal rat lung development

BB1 was recently cloned from the WI-38 human fetal lung cell line. Human BB 1 (hBB1) is expressed by multiple tissues, including lung. Because inhibiti on of BB1 translation using antisense oligodeoxynucleotides resulted in pre vention of G1 traversal in cultured cells, we hypothesized that BB1 gene ex pression would be regulated during lung development with greater expression during periods of active lung growth. lo gain insight into the expression of BB1 during lung development, a rat BB1 (rBB1) homologue was cloned and u sed in Northern hybridization analyses and in situ hybridization histochemi stry (ISHH), Northern hybridization analyses of fetal and postnatal rat lun g demonstrate that rBB1 RNA abundance is relatively low on fetal days E17 t hrough E19, with a small peak of expression occurring on fetal day E20, the n increases at birth with peak expression in adult lung. ISHH correlates wi th the Northern hybridization data and reveals rBB1 RNA expression througho ut lung from E17 to E21 in both epithelium and mesenchyme. In postnatal lun g, more intense expression of BB1 was observed than in fetal lung, localizi ng BB1 transcripts to proximal and dietal airways and mesenchymal cells sur rounding 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 PC NA-positive cells were detected, but intense BB1 expression was detected in airway epithelium and surrounding mesenchyme. These studies demonstrate de velopmental regulation of BB1 during lung development. The findings are con sistent with BB1 action in cell growth-related processes of fetal and early postnatal lung; however, the distribution of BB1 expression in relation to PCNA localisation suggests that BBI participates in cellular functions in addition to cell proliferation.