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Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma.
- Source :
-
International journal of cancer [Int J Cancer] 2012 Mar 15; Vol. 130 (6), pp. 1329-37. Date of Electronic Publication: 2011 Jul 21. - Publication Year :
- 2012
-
Abstract
- Renal clear cell carcinoma (RCCC) is the most frequent subpopulation of renal cell carcinoma and is derived from the proximal uriniferous tubules. We have previously reported that an actin-binding protein, 4.1B/DAL-1, is expressed in renal proximal tubules, whereas it is inactivated in 45% of RCCC by promoter methylation. In the lung and several epithelial tissues, 4.1B is shown to associate with a tumor suppressor protein, CADM1, belonging to the immunoglobulin-superfamily cell adhesion molecules. Here, we demonstrate by immunohistochemistry that another member of the CADM-family protein, CADM4, as well as 4.1B is expressed specifically in human proximal tubules, while CADM1 and 4.1N, another member of the 4.1 proteins, are expressed in the distal tubules. Immunoprecipitation analysis coupled with Western blotting revealed that CADM4 associated with 4.1B, while CADM1 associated with 4.1N in the lysate from normal human kidney, implicating that a cascade of CADM4 and 4.1B plays an important role in normal cell adhesion of the proximal tubules. On the other hand, CADM4 expression was lost or markedly reduced in 7 of 10 (70%) RCC cell lines and 28 of 40 (70%) surgically resected RCCC, including 10 of 16 (63%) tumors with T1a. CADM4 expression was more preferentially lost in RCCC with vascular infiltration (p = 0.04), suggesting that loss of CADM4 is involved in tumor invasion. Finally, introduction of CADM4 into an RCC cell line, 786-O, dramatically suppressed tumor formation in nude mice. These findings suggest that CADM4 is a novel tumor suppressor candidate in RCCC acting with its binding partner 4.1B.<br /> (Copyright © 2011 UICC.)
- Subjects :
- Animals
Carcinoma, Renal Cell metabolism
Carcinoma, Renal Cell pathology
Cell Adhesion genetics
Cell Adhesion Molecule-1
Cell Adhesion Molecules biosynthesis
Cell Line, Tumor
Cytoskeletal Proteins biosynthesis
Cytoskeletal Proteins genetics
Female
Genes, Tumor Suppressor
Humans
Immunoglobulins biosynthesis
Immunohistochemistry methods
Kidney Neoplasms metabolism
Kidney Neoplasms pathology
Kidney Tubules, Distal metabolism
Kidney Tubules, Distal pathology
Kidney Tubules, Proximal metabolism
Kidney Tubules, Proximal pathology
Membrane Glycoproteins
Membrane Proteins biosynthesis
Membrane Proteins genetics
Membrane Proteins metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Neuropeptides biosynthesis
Neuropeptides genetics
Protein Binding genetics
Protein Interaction Domains and Motifs
Carcinoma, Renal Cell genetics
Cell Adhesion Molecules genetics
Immunoglobulins genetics
Kidney Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 130
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 21544807
- Full Text :
- https://doi.org/10.1002/ijc.26160