Ectopic expression of CDX2 was reported more than 85% of the human patients with Acute myeloid leukemia (AML). Ectopic expression of Cdx2 in murine bome marrow induced AML in mice and upregulate Hox genes in bone marrow progenitors.[3][4][5]
Biomarker for intestinal cancer
CDX2 is also used in diagnostic surgical pathology as a marker for gastrointestinal differentiation, especially colorectal.[6]
Possible use in stem cell research
This gene (or, more specifically, the equivalent gene in humans) has come up in the proposal by the President's Council on Bioethics, as a solution to the stem cell controversy.[7] According to one of the plans put forth, by deactivating the gene, it would not be possible for a properly organized embryo to form, thus providing stem cells without requiring the destruction of an embryo.[8] Other genes that have been proposed for this purpose include Hnf4, which is required for gastrulation.[7][9]
References
^ German MS, Wang J, Fernald AA, Espinosa R, Le Beau MM, Bell GI (November 1994). "Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13". Genomics24 (2): 403–4. doi:10.1006/geno.1994.1639. PMID 7698771.
^ Liu Q, Teh M, Ito K, Shah N, Ito Y, Yeoh KG (December 2007). "CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer". Mod. Pathol.20 (12): 1286–97. doi:10.1038/modpathol.3800968. PMID 17906616.
^ Hurlbut WB (2007). "Ethics and embryonic stem cell research: altered nuclear transfer as a way forward". BioDrugs21 (2): 79–83. PMID 17402791.
Further reading
German MS, Wang J, Fernald AA, et al. (1995). "Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13.". Genomics24 (2): 403–4. doi:10.1006/geno.1994.1639. PMID 7698771.
Suh E, Chen L, Taylor J, Traber PG (1994). "A homeodomain protein related to caudal regulates intestine-specific gene transcription.". Mol. Cell. Biol.14 (11): 7340–51. PMID 7935448.
Inoue H, Riggs AC, Tanizawa Y, et al. (1996). "Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene.". Diabetes45 (6): 789–94. PMID 8635654.
Mallo GV, Rechreche H, Frigerio JM, et al. (1997). "Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis.". Int. J. Cancer74 (1): 35–44. PMID 9036867.
Chawengsaksophak K, James R, Hammond VE, et al. (1997). "Homeosis and intestinal tumours in Cdx2 mutant mice.". Nature386 (6620): 84–7. doi:10.1038/386084a0. PMID 9052785.
Walters JR, Howard A, Rumble HE, et al. (1997). "Differences in expression of homeobox transcription factors in proximal and distal human small intestine.". Gastroenterology113 (2): 472–7. PMID 9247466.
Drummond F, Putt W, Fox M, Edwards YH (1998). "Cloning and chromosome assignment of the human CDX2 gene.". Ann. Hum. Genet.61 (Pt 5): 393–400. doi:10.1046/j.1469-1809.1997.6150393.x. PMID 9459001.
Yamamoto H, Miyamoto K, Li B, et al. (1999). "The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine.". J. Bone Miner. Res.14 (2): 240–7. PMID 9933478.
Lorentz O, Suh ER, Taylor JK, et al. (1999). "CREB-binding [corrected] protein interacts with the homeodomain protein Cdx2 and enhances transcriptional activity.". J. Biol. Chem.274 (11): 7196–9. PMID 10066780.
Hussain MA, Habener JF (1999). "Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator.". J. Biol. Chem.274 (41): 28950–7. PMID 10506141.
Mitchelmore C, Troelsen JT, Spodsberg N, et al. (2000). "Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene.". Biochem. J.346 Pt 2: 529–35. PMID 10677375.
Sivagnanasundaram S, Islam I, Talbot I, et al. (2001). "The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis.". Br. J. Cancer84 (2): 218–25. doi:10.1054/bjoc.2000.1544. PMID 11161380.
Rings EH, Boudreau F, Taylor JK, et al. (2001). "Phosphorylation of the serine 60 residue within the Cdx2 activation domain mediates its transactivation capacity.". Gastroenterology121 (6): 1437–50. PMID 11729123.
Hinoi T, Tani M, Lucas PC, et al. (2001). "Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon.". Am. J. Pathol.159 (6): 2239–48. PMID 11733373.
Mizoshita T, Inada K, Tsukamoto T, et al. (2002). "Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa--with special emphasis on participation in intestinal metaplasia of the human stomach.". Gastric Cancer4 (4): 185–91. PMID 11846061.
Eda A, Osawa H, Yanaka I, et al. (2002). "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia.". J. Gastroenterol.37 (2): 94–100. PMID 11871772.
Qualtrough D, Hinoi T, Fearon E, Paraskeva C (2002). "Expression of CDX2 in normal and neoplastic human colon tissue and during differentiation of an in vitro model system.". Gut51 (2): 184–90. PMID 12117877.
Moucadel V, Totaro MS, Dell CD, et al. (2002). "The homeobox gene Cdx1 belongs to the p53-p21(WAF)-Bcl-2 network in intestinal epithelial cells.". Biochem. Biophys. Res. Commun.297 (3): 607–15. PMID 12270138.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A.99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Song BL, Qi W, Wang CH, et al. (2003). "Preparation of an anti-Cdx-2 antibody for analysis of different species Cdx-2 binding to acat2 promoter.". Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao35 (1): 6–12. PMID 12518221.