title: A conserved tissue-specific homeodomain-less isoform of MEIS1 is downregulated in colorectal cancer.
abstract: Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing expression of two previously described isoforms, as well as two novel Meis1 products. A 32 kD Meis1 product was expressed in the nuclei of non-epithelial cells in the stomach and colon, while a 27 kD product was expressed in the cytoplasm of epithelial cells in the proximal colon. Our data suggest that the 27 kD and 32 kD Meis1 proteins are both forms of the Meis1d protein, a homeodomain-less isoform whose transcript was previously identified in cDNA screens. Both the MEIS1D transcript and protein were expressed in human colon mucosa. Expression of the MEIS1D protein was downregulated in 83% (10/12) of primary colorectal cancer samples compared to matched normal mucosa, indicating that MEIS1D is a biomarker of colorectal tumorigenesis. The decreased expression of MEIS1D in colon tumors also suggests that this conserved homeodomain-less isoform may act as a tumor suppressor in human colorectal cancer.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Crist
authors.forename: Jacquelyn J
authors.initials: JJ
authors.lastname: Roth
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Buchberg
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002432:Cecum / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D020033:Protein Isoforms