This Article Order Full text via Infotrieve Services 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 Woodman, A. C. Articles by Tarin, D. Search for Related Content PubMed PubMed Citation Articles by Woodman, A. C. Articles by Tarin, D.

American Journal of Pathology, Vol 149, 1519-1530, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Analysis of anomalous CD44 gene expression in human breast, bladder, and colon cancer and correlation of observed mRNA and protein isoforms

AC Woodman, M Sugiyama, K Yoshida, T Sugino, A Borgya, S Goodison, Y Matsumura and D Tarin
Nuffield Department of Pathology and Bacteriology, University of Oxford, John Radcliffe Hospital, United Kingdom.

Many studies have now demonstrated disorganized overexpression of the CD44 gene in various types of human malignant tumors, and this abnormality has emerged as an interesting candidate marker for early cancer diagnosis. The purpose of this work was to analyze and compare the patterns of transcription and translation of this gene in human breast (ZR75-1; MDAMB-435 clone 4A4) and colon (HT29) tumor cell lines and in tumors of the breast, bladder, and colon, with the aim of identifying the most suitable analyte for diagnostic purposes. Transcription was studied by reverse transcription-polymerase chain reaction using CD44-specific primers and probes complementary to exons in the standard (exons 3 to 5 and 16 to 18) and variably expressed regions of this gene (exons 7, 8, 10, 11, and 15). Translation was investigated by Western blot analysis and immunohistochemistry using monoclonal antibodies specific to the standard form of CD44 and to the products of the same variant exons. Southern blot hybridization analysis of the reverse transcription-polymerase chain reaction products showed a large number of CD44 transcripts in tumor cells. Direct comparison of these Southern blots with Western blots on matched tumor-cell-line extracts indicated that most of the diverse mRNA isoforms did not detectably translate into proteins. However, immunohistochemistry of normal and malignant breast (n = 17 and 23, respectively), bladder (n = 5 and 19), and colon (n = 19 and 19) tissue specimens showed increased staining of CD44 standard and CD44 variant proteins in the carcinoma cells. Combination of this information with the data from reverse transcription-polymerase chain reaction and Western blot analysis indicates that the overexpression at the protein level involves only a minority of the aberrant RNA transcripts. We conclude that the development of methods for the accurate quantitation of over-abundant CD44 RNA species in clinical samples offers the most promising approach to improved early diagnosis of malignancy using this new marker.

This article has been cited by other articles:

				Y. Wang, R. Wu, K. R. Cho, K. A. Shedden, T. J. Barder, and D. M. Lubman Classification of Cancer Cell Lines Using an Automated Two-dimensional Liquid Mapping Method with Hierarchical Clustering Techniques Mol. Cell. Proteomics, January 1, 2006; 5(1): 43 - 52. [Abstract] [Full Text] [PDF]

				I. Okamoto, H. Tsuiki, L. C. Kenyon, A. K. Godwin, D. R. Emlet, M. Holgado-Madruga, I. S. Lanham, C. J. Joynes, K. T. Vo, A. Guha, et al. Proteolytic Cleavage of the CD44 Adhesion Molecule in Multiple Human Tumors Am. J. Pathol., February 1, 2002; 160(2): 441 - 447. [Abstract] [Full Text] [PDF]

				V. Urquidi, D. Sloan, K. Kawai, D. Agarwal, A. C. Woodman, D. Tarin, and S. Goodison Contrasting Expression of Thrombospondin-1 and Osteopontin Correlates with Absence or Presence of Metastatic Phenotype in an Isogenic Model of Spontaneous Human Breast Cancer Metastasis Clin. Cancer Res., January 1, 2002; 8(1): 61 - 74. [Abstract] [Full Text] [PDF]

				Y. Ohene-Abuakwa and M. Pignatelli Adhesion Molecules as Diagnostic Tools in Tumor Pathology International Journal of Surgical Pathology, July 1, 2000; 8(3): 191 - 200. [Abstract] [PDF]

				P. HERRLICH, H. MORRISON, J. SLEEMAN, V. ORIAN-ROUSSEAU, H. KONIG, S. WEG-REMERS, and H. PONTA CD44 Acts Both as a Growth- and Invasiveness-Promoting Molecule and as a Tumor-Suppressing Cofactor Ann. N.Y. Acad. Sci., June 1, 2000; 910(1): 106 - 120. [Abstract] [Full Text] [PDF]

				A. C. Woodman, S. Goodison, M. Drake, J. Noble, and D. Tarin Noninvasive Diagnosis of Bladder Carcinoma by Enzyme-linked Immunosorbent Assay Detection of CD44 Isoforms in Exfoliated Urothelia Clin. Cancer Res., June 1, 2000; 6(6): 2381 - 2392. [Abstract] [Full Text]

				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]

				S. Goodison, K. Yoshida, M. Churchman, and D. Tarin Multiple Intron Retention Occurs in Tumor Cell CD44 mRNA Processing Am. J. Pathol., October 1, 1998; 153(4): 1221 - 1228. [Abstract] [Full Text] [PDF]

				X. Roca, J. L. Mate, A. Ariza, A. M. Munoz-Marmol, C. von Uexkull-Guldeband, I. Pellicer, J. J. Navas-Palacios, and M. Isamat CD44 Isoform Expression Follows Two Alternative Splicing Pathways in Breast Tissue Am. J. Pathol., July 1, 1998; 153(1): 183 - 190. [Abstract] [Full Text] [PDF]