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Am. J. Respir. Cell Mol. Biol., Volume 19, Number 4, October, 1998 554-562

Expression of Heterogeneous Nuclear Ribonucleoprotein A2/B1 Changes with Critical Stages of Mammalian Lung Development

Luis M. Montuenga, Jun Zhou, Ingalill Avis, Michele Vos, Alfredo Martinez, Frank Cuttitta, Anthony M. Treston, Mary Sunday, and James L. Mulshine

Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Department of Histology and Pathology, University of Navarra, Pamplona, Spain; and Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Recent reports have demostrated a link between expression of members of the family of heterogeneous nuclear ribonucleoproteins (hnRNPs) and cancer. Overexpression of hnRNP A2/B1 correlated with the eventual development of lung cancer in three different clinical cohorts. We have studied the expression of hnRNP A2/B1 messenger RNA (mRNA) and protein during mammalian development. The expression of hnRNP A2/B1 mRNA and protein are parallel but change dynamically during critical periods in mouse pulmonary development. hnRNP A2/B1 is first detected in the lung in the early pseudoglandular period, peaks at the beginning of the canalicular period, and remains high during the saccular (alveolar) period. In mouse and rat, hnRNP A2/B1 expression is first evident in the earliest lung buds. As lung development progresses, the cuboidal epithelial cells of the distal primitive alveoli show high levels of the ribonucleoprotein, which is almost undetectable in the proximal conducting airways. The expression of hnRNP A2/ B1 is restricted in mature lung. Similar dynamic pattern of expression through lung development was also found in rat and human lung. Upregulated expression of hnRNP A2/B1 at critical periods of lung development was comparable to the level of expression found in lung cancers and preneoplastic lesions and is consistent with hnRNP A2/B1 overexpression playing an oncodevelopmental role.




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