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 Ermak, G. Articles by Figge, J. Search for Related Content PubMed PubMed Citation Articles by Ermak, G. Articles by Figge, J.

Restricted Patterns of CD44 Variant Exon Expression in Human Papillary Thyroid Carcinoma¹

Departments of Medicine [J. F.], Surgery [L. R.], and Pathology [G. E., T. J., J. S. R., J. F.], Albany Medical College, Albany, New York 12208, and Department of Biomedical Sciences, State University of New York, Albany, New York 12201 [J. F.]

CD44 is a polymorphic family of cell surface proteoglycans and glycoproteins implicated in cell-cell and cell-matrix adhesion interactions, cell migration, and tumor metastasis. CD44 exists as a standard form and as multiple isoforms arising from alternative splicing of variant exons (termed v1–v10) encoding parts of the extracellular domain. We demonstrated previously that papillary thyroid carcinomas exhibit aberrant patterns of alternative CD44 mRNA splicing (G. Ermak et al., Cancer Res., 55: 4594–4598, 1995). In the present report, we use reverse transcription-PCR using a new high-performance polymerase formulation (Ex Taq; TaKaRa Shuzo Co., Ltd., Otsu, Japan), followed by Southern hybridization, and demonstrate that alternative exon usage in papillary thyroid carcinomas is restricted primarily to exons v6, v7, v8, v9, and v10, with weak expression of v3. Expression of v8 is tightly linked to v9 and closely related to v10 expression. Also, v6 and v7 expression are closely related. Papillary thyroid cancers exhibit a marked increase in specific mRNA species containing combinations of exons v6 to v10. Several isoforms found in papillary cancers are not detectable in histologically normal tissue derived from the corresponding contralateral thyroid lobes. Examples include a 750-bp v6- and v7-containing PCR product and a 650-bp v8- and v9-containing PCR product. Finally, a novel 530-bp PCR product was discovered and shown to contain a subsegment from exon 4 joined to a subsegment of exon 13 (v8), followed by the complete sequence of exons 14 (v9) and 15 (v10). This novel isoform was present in both the papillary cancers and contralateral tissues. In conclusion, papillary thyroid cancers exhibit specific patterns of aberrant alternative CD44 splicing, distinguishing them from histologically normal thyroid tissue.

¹ This study was supported by a grant from the Lucille P. Markey Charitable Trust (to J. F.) and by a grant from BASF Corporation.

² To whom requests for reprints should be addressed, at Department of Medicine, Division of Endocrinology and Metabolism, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208. Phone: (518) 262-5185; Fax: (518) 262-6251.

Received 10/ 4/95. Accepted 12/27/95.

This article has been cited by other articles:

				V. Guarino, P. Faviana, G. Salvatore, M. D. Castellone, A. M. Cirafici, V. De Falco, A. Celetti, R. Giannini, F. Basolo, R. M. Melillo, et al. Osteopontin Is Overexpressed in Human Papillary Thyroid Carcinomas and Enhances Thyroid Carcinoma Cell Invasiveness J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5270 - 5278. [Abstract] [Full Text] [PDF]

				G. ERMAK, C. D. HARRIS, and K. J. A. DAVIES The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress FASEB J, June 1, 2002; 16(8): 814 - 824. [Abstract] [Full Text] [PDF]

				J. Lukas, D.-Q. Gao, M. Keshmeshian, W.-H. Wen, D. Tsao-Wei, S. Rosenberg, and M. F. Press Alternative and Aberrant Messenger RNA Splicing of the mdm2 Oncogene in Invasive Breast Cancer Cancer Res., April 1, 2001; 61(7): 3212 - 3219. [Abstract] [Full Text]

				A. Nandi, P. Estess, and M. H. Siegelman Hyaluronan Anchoring and Regulation on the Surface of Vascular Endothelial Cells Is Mediated through the Functionally Active Form of CD44 J. Biol. Chem., May 12, 2000; 275(20): 14939 - 14948. [Abstract] [Full Text] [PDF]

				A. Gasbarri, M. P. Martegani, F. Del Prete, T. Lucante, P. G. Natali, and A. Bartolazzi Galectin-3 and CD44v6 Isoforms in the Preoperative Evaluation of Thyroid Nodules J. Clin. Oncol., November 1, 1999; 17(11): 3494 - 3502. [Abstract] [Full Text] [PDF]

				K. Aogi, K. Kitahara, V. Urquidi, D. Tarin, and S. Goodison Comparison of Telomerase and CD44 Expression as Diagnostic Tumor Markers in Lesions of the Thyroid Clin. Cancer Res., October 1, 1999; 5(10): 2790 - 2797. [Abstract] [Full Text] [PDF]