Published online before print July 2, 2009

This Article Full Text Full Text (PDF) All Versions of this Article: ajpath.2009.081135v1 175/2/461    most recent Purchase Article View Shopping Cart 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 Körner, M. Articles by Miller, L. J. Search for Related Content PubMed PubMed Citation Articles by Körner, M. Articles by Miller, L. J.

(American Journal of Pathology. 2009;175:461-472.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.081135

Review

Alternative Splicing of Pre-mRNA in Cancer

Focus on G Protein-Coupled Peptide Hormone Receptors

Meike Körner^* and Laurence J. Miller

From the Mayo Clinic,^* Cancer Center and Department of Molecular Pharmacology and Experimental Therapeutics, Scottsdale, Arizona; and the Institute of Pathology of the University of Berne, Berne, Switzerland

Through alternative splicing, multiple different transcripts can be generated from a single gene. Alternative splicing represents an important molecular mechanism of gene regulation in physiological processes such as developmental programming as well as in disease. In cancer, splicing is significantly altered. Tumors express a different collection of alternative spliceoforms than normal tissues. Many tumor-associated splice variants arise from genes with an established role in carcinogenesis or tumor progression, and their functions can be oncogenic. This raises the possibility that products of alternative splicing play a pathogenic role in cancer. Moreover, cancer-associated spliceoforms represent potential diagnostic biomarkers and therapeutic targets. G protein-coupled peptide hormone receptors provide a good illustration of alternative splicing in cancer. The wild-type forms of these receptors have long been known to be expressed in cancer and to modulate tumor cell functions. They are also recognized as attractive clinical targets. Recently, splice variants of these receptors have been increasingly identified in various types of cancer. In particular, alternative cholecystokinin type 2, secretin, and growth hormone-releasing hormone receptor spliceoforms are expressed in tumors. Peptide hormone receptor splice variants can fundamentally differ from their wild-type receptor counterparts in pharmacological and functional characteristics, in their distribution in normal and malignant tissues, and in their potential use for clinical applications.

This article has been cited by other articles:

				S. Makawita and E. P. Diamandis The Bottleneck in the Cancer Biomarker Pipeline and Protein Quantification through Mass Spectrometry-Based Approaches: Current Strategies for Candidate Verification Clin. Chem., February 1, 2010; 56(2): 212 - 222. [Abstract] [Full Text] [PDF]