This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oyama, F. Articles by Sekiguchi, K. Search for Related Content PubMed PubMed Citation Articles by Oyama, F. Articles by Sekiguchi, K.

Oncodevelopmental Regulation of the Alternative Splicing of Fibronectin Pre-Messenger RNA in Human Lung Tissues¹

Institute for Comprehensive Medical Science, Fujita Health University School of Medicine, Toyoake, Aichi 470-11 [F. O., K. T., K. S.], and Pathology Division, National Cancer Center Research Institute, Tsujiji, Chuo-ku, Tokyo 104 [S. H., Y. S.], Japan

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.

¹ This work was supported by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan, from Fujita Health University, and from the Naito Foundation.

² To whom requests for reprints should be addressed.

Received 9/25/89. Accepted 11/ 2/89.

This article has been cited by other articles:

				S. Astrof, D. Crowley, E. L. George, T. Fukuda, K. Sekiguchi, D. Hanahan, and R. O. Hynes Direct Test of Potential Roles of EIIIA and EIIIB Alternatively Spliced Segments of Fibronectin in Physiological and Tumor Angiogenesis Mol. Cell. Biol., October 1, 2004; 24(19): 8662 - 8670. [Abstract] [Full Text] [PDF]

				M. Midulla, R. Verma, M. Pignatelli, M. A. Ritter, N. S. Courtenay-Luck, and A. J. T. George Source of Oncofetal ED-B-containing Fibronectin: Implications of Production by Both Tumor and Endothelial Cells Cancer Res., January 1, 2000; 60(1): 164 - 169. [Abstract] [Full Text]

				D. Dubin, J. H. Peters, L. F. Brown, B. Logan, K. C. Kent, B. Berse, S. Berven, B. Cercek, B. G. Sharifi, R. E. Pratt, et al. Balloon Catheterization Induces Arterial Expression of Embryonic Fibronectins Arterioscler Thromb Vasc Biol, November 1, 1995; 15(11): 1958 - 1967. [Abstract] [Full Text]

				H. Mardon, R. Grant, K. Grant, and H Harris Fibronectin splice variants are differentially incorporated into the extracellular matrix of tumorigenic and non-tumorigenic hybrids between normal fibroblasts and sarcoma cells J. Cell Sci., January 3, 1993; 104(3): 783 - 792. [Abstract] [PDF]

				H. J. Mardon and G. Sebastio Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5 J. Cell Sci., October 1, 1992; 103(2): 423 - 433. [Abstract] [PDF]