Oncodevelopmental regulation of the alternative splicing of fibronectin pre-messenger RNA in human lung tissues

Alternative splicing of fibronectin pre-mRNA at the ED-A region has been shown to be deregulated in malignant human liver tumors (F. Oyama et al., J. Biol. Chem., 264: 10331-10334, 1989). In order to extend this observation to other human cancers, we investigated the splicing patterns of fibronectin pre-mRNA at both ED-A and ED-B regions in normal, fetal, and cancerous lung tissues. Unlike in the liver, the ED-A+ mRNA was constitutively expressed in the lung irrespective of ontogenic or oncogenic stages. Although fetal tissues expressed the ED-A+ mRNA slightly more than did adult tissues, there was virtually no significant difference between malignant and nonmalignant tissues in the level of the ED-A+ mRNA. In contrast, significant expression of the ED-B+ mRNA was observed with fetal and cancerous tissues but not with normal adult tissues. Increased expression of the ED-B+ mRNA was associated with all types of lung cancer including adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma. These results indicate that it is the ED-B, but not the ED-A, region where the alternative splicing of fibronectin pre-mRNA is oncodevelopmentally regulated in the lung. Our results also suggest that deregulation of the tissue-specific alternative splicing of fibronectin pre-mRNA is not a unique phenotype of liver cancer but rather a general feature of naturally occurring human cancer.