Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium
- 169 Downloads
Recently, we have reported that the protein 4.1B immunolocalization occurred only in matured columnar epithelial cells of normal rat intestines. This finding suggested that protein 4.1B expression could be examined for a possible change during neoplastic transformation of the intestinal mucosa. In the present study, we first present the distribution of mouse protein 4.1B in normal intestinal epithelial cells and tumor cells using the adenomatous polyposis coli (Apc) mutant mouse model. A low level of protein 4.1B expression coincided with the phenotypic transition to carcinoma. To examine the protein 4.1B expression in human intestinal mucosa, we used another antibody against an isoform of the human protein 4.1B, DAL-1 (differentially expressed adenocarcinoma of the lung). Human DAL-1 was also expressed in matured epithelial cells in human colons, with a definite expression gradient along the crypt axis. In human colorectal cancer cells, however, DAL-1 expression was not detected. These results suggest that mouse protein 4.1B and human DAL-1 might have a striking analogy of functions, which may be integrally involved in epithelial proliferation. We propose that loss of protein 4.1B/DAL-1 expression might be a marker of intestinal tumors, indicative of a tumor suppressor function in the intestinal mucosa.
KeywordsProtein 4.1B DAL-1 Mutant mouse strain Intestinal neoplasm Colorectal cancer
The authors would like to thank Dr. Riccardo Fodde, Department of Pathology, Josephone Nefkens Institute, Erasmus University Medical Center, for sending us the intestinal tissues of Apc mutant model mouse, Apc+/Apc1638 N. The authors also thank Drs. Takeshi Baba, Yasuhisa Fujii, and Zagreb Zea-Aragon, Department of Anatomy, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, for their constructive comments on this work.
- Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ Jr, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Tsukita S, Arpin M, Louvard D, Tonks NK, Anderson JM, Fanning AS, Bryant PJ, Woods DF, Hoover KB (1998) The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem Sci 23:281–282CrossRefPubMedGoogle Scholar
- Parra M, Gascard P, Walensky LD, Gimm JA, Blackshaw S, Chan N, Takakuwa Y, Berger T, Lee G, Chasis JA, Snyder SH, Mohandas N, Conboy JG (2000) Molecular and functional characterization of protein 4.1B, a novel member of protein 4.1 family with high level, focal expression in brain. J Biol Chem 275:3247–3255CrossRefPubMedGoogle Scholar
- Perry A, Cai DX, Scheithauer BW, Swanson PE, Lohse CM, Newsham IF, Weaver A, Gutmann DH (2000) Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. J Neuropathol Exp Neurol 59:872–879PubMedGoogle Scholar
- Perry A, Giannini C, Raghavan R, Scheithauer BW, Banerjee R, Margraf L, Bowers DC, Lytle RA, Newsham IF, Gutmann DH (2001) Aggressive phenotypic and genotypic features in pediatric and NF-2 associated meningiomas: a clinicopathologic study of 53 cases. J Neuropathol Exp Neurol 60:994–1003PubMedGoogle Scholar
- Stewart BW, Kleihues P (2003) World cancer report. IARC Press, LyonGoogle Scholar
- Yu Y, Khan J, Khanna C, Helman L, Meltzer PS, Merlino G (2004) Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med 10:175–181Google Scholar
- Zhang S, Mizutani A, Hisatsune C, Higo T, Bannai H, Nakayama T, Hattori M, Mikoshiba K (2003) Protein 4.1 N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells. J Biol Chem 278:4048–4056CrossRefPubMedGoogle Scholar