|
|
|
Research Papers
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Abstract
The analysis of human colorectal tumors has revealed frequent loss of heterozygosity (LOH) of the long arm of chromosome 18. A novel gene, DCC (deleted in colorectal cancer), located within the region of LOH on chromosome 18q was identified and has been implicated as a tumor suppressor gene. We have now shown that DCC encodes a membrane-bound protein of the immunoglobulin-CAM family, as demonstrated by cell-surface labeling, immunohistochemical analysis, and sequencing of cDNA clones. The DCC protein was found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lacked DCC expression and loss of a chromosome 18q allele was often accompanied by loss of DCC expression in colon tumors. These results provide evidence that DCC encodes a cell surface-localized protein and emphasize the inverse relationship between differentiation and tumorigenesis.
This article has been cited by other articles:
![]() |
A. Suli, N. Mortimer, I. Shepherd, and C.-B. Chien Netrin/DCC Signaling Controls Contralateral Dendrites of Octavolateralis Efferent Neurons J. Neurosci., December 20, 2006; 26(51): 13328 - 13337. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. Carvalho, A. Chuang, W.-W. Jiang, J. Lee, S. Begum, L. Poeta, M. Zhao, C. Jeronimo, R. Henrique, C. S. Nayak, et al. Deleted in Colorectal Cancer Is a Putative Conditional Tumor-Suppressor Gene Inactivated by Promoter Hypermethylation in Head and Neck Squamous Cell Carcinoma Cancer Res., October 1, 2006; 66(19): 9401 - 9407. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. V. Negri, A. Wotherspoon, D. Cunningham, A. R. Norman, G. Chong, and P. J. Ross Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer Ann. Onc., August 1, 2005; 16(8): 1305 - 1310. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Mehlen and E. R. Fearon Role of the Dependence Receptor DCC in Colorectal Cancer Pathogenesis J. Clin. Oncol., August 15, 2004; 22(16): 3420 - 3428. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. BREDESEN, P. MEHLEN, and S. RABIZADEH Apoptosis and Dependence Receptors: A Molecular Basis for Cellular Addiction Physiol Rev, April 1, 2004; 84(2): 411 - 430. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ikeda, Y. Shimizu, M. Fujimori, Y. Ishizaki, T. Kurihara, Y. Ojima, M. Okajima, and T. Asahara Immunohistochemical and Mutational Analyses of {beta}-catenin, Ki-ras, and p53 in Two Subtypes of Colorectal Mucinous Carcinoma Clin. Cancer Res., November 15, 2003; 9(15): 5660 - 5665. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Taniguchi, S.-H. Kim, and S. S. Sisodia Presenilin-dependent "{gamma}-Secretase" Processing of Deleted in Colorectal Cancer (DCC) J. Biol. Chem., August 15, 2003; 278(33): 30425 - 30428. [Abstract] [Full Text] [PDF] |
||||
![]() |
A Hara, M Saegusa, T Mikami, and I Okayasu Loss of DCC expression in astrocytomas: relation to p53 abnormalities, cell kinetics, and survival J. Clin. Pathol., November 1, 2001; 54(11): 860 - 865. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Manitt, M. A. Colicos, K. M. Thompson, E. Rousselle, A. C. Peterson, and T. E. Kennedy Widespread Expression of Netrin-1 by Neurons and Oligodendrocytes in the Adult Mammalian Spinal Cord J. Neurosci., June 1, 2001; 21(11): 3911 - 3922. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Forcet, X. Ye, L. Granger, V. Corset, H. Shin, D. E. Bredesen, and P. Mehlen The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation PNAS, February 22, 2001; (2001) 51378298. [Abstract] [Full Text] |
||||
![]() |
J. A. Meyerhardt, K. Caca, B. C. Eckstrand, G. Hu, C. Lengauer, S. Banavali, A. T. Look, and E. R. Fearon Netrin-1: Interaction with Deleted in Colorectal Cancer (DCC) and Alterations in Brain Tumors and Neuroblastomas Cell Growth Differ., January 1, 1999; 10(1): 35 - 42. [Abstract] [Full Text] |
||||
![]() |
K. L. Bennett, J. Bradshaw, T. Youngman, J. Rodgers, B. Greenfield, A. Aruffo, and P. S. Linsley Deleted in Colorectal Carcinoma (DCC) Binds Heparin via Its Fifth Fibronectin Type III Domain J. Biol. Chem., October 24, 1997; 272(43): 26940 - 26946. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Hu, S. Zhang, M. Vidal, J. L. Baer, T. Xu, and E. R. Fearon Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway Genes & Dev., October 15, 1997; 11(20): 2701 - 2714. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-S. Kang, M. Gao, J. L. Feinleib, P. D. Cotter, S. N. Guadagno, and R. S. Krauss CDO: An Oncogene-, Serum-, and Anchorage-regulated Member of the Ig/Fibronectin Type III Repeat Family J. Cell Biol., July 14, 1997; 138(1): 203 - 213. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Shibata, M. A. Reale, P. Lavin, M. Silverman, E. R. Fearon, G. Steele, J. M. Jessup, M. Loda, and I. C. Summerhayes The DCC Protein and Prognosis in Colorectal Cancer N. Engl. J. Med., December 5, 1996; 335(23): 1727 - 1732. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Forcet, X. Ye, L. Granger, V. Corset, H. Shin, D. E. Bredesen, and P. Mehlen The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation PNAS, March 13, 2001; 98(6): 3416 - 3421. [Abstract] [Full Text] [PDF] |
||||