Montuenga L M, Zhou J, Avis I, Vos M, Martinez A, Cuttitta F, Treston A M, Sunday M, Mulshine J L
Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Am J Respir Cell Mol Biol. 1998 Oct;19(4):554-62. doi: 10.1165/ajrcmb.19.4.3185.
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.
最近的报告已证明异质性核核糖核蛋白(hnRNPs)家族成员的表达与癌症之间存在联系。在三个不同的临床队列中,hnRNP A2/B1的过表达与肺癌的最终发展相关。我们研究了hnRNP A2/B1信使核糖核酸(mRNA)和蛋白质在哺乳动物发育过程中的表达情况。hnRNP A2/B1 mRNA和蛋白质的表达是平行的,但在小鼠肺发育的关键时期会动态变化。hnRNP A2/B1最早在假腺期早期的肺中被检测到,在小管期开始时达到峰值,并在囊状(肺泡)期保持高水平。在小鼠和大鼠中,hnRNP A2/B1的表达最早在最早的肺芽中明显可见。随着肺发育的进展,远端原始肺泡的立方上皮细胞显示出高水平的核糖核蛋白,而在近端传导气道中几乎检测不到。hnRNP A2/B1的表达在成熟肺中受到限制。在大鼠和人肺中也发现了在肺发育过程中类似的动态表达模式。在肺发育关键时期hnRNP A2/B1表达上调与在肺癌和癌前病变中发现的表达水平相当,这与hnRNP A2/B1过表达发挥肿瘤发生发展作用是一致的。