| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892
The isolation of genes involved in cancer development is critical for uncovering the molecular basis of cancer. We report here the isolation of the full-length cDNA and chromosomal localization of a new gene frequently deleted in liver cancer (DLC-1) that was identified by representational difference analysis. Loss of heterozygosity was detected for DLC-1 in 7 of 16 primary hepatocellular carcinomas (HCCs) and in 10 of 11 HCC cell lines. Although mRNA for DLC-1 was expressed in all normal human tissues, it was not expressed in 4 of 14 HCC cell lines. Full-length cDNA for DLC-1 of 3800 bp encodes a protein of 1091 amino acids, has 86% homology with rat p122 RhoGAP gene, and was localized by fluorescence in situ hybridization on chromosome 8 at bands p21.3–22. Deletions on the short arm of chromosome 8 are recurrent in liver, breast, lung, and prostate cancers, suggesting the presence of tumor suppressor genes. DLC-1 may be a tumor suppressor gene in liver cancer as well as in other cancers.
1 To whom requests for reprints should be addressed, at National Cancer Institute, Building 37, Room 3C28, 37 Convent Drive MSC4255, Bethesda, MD 20892-4255. Phone: (301) 496-5688; Fax: (301) 496-0734.
Received 1/ 8/98. Accepted 3/18/98.
This article has been cited by other articles:
|
|
 |
|
  D. Zhong, J. Zhang, S. Yang, U. J. K. Soh, J. P. Buschdorf, Y. T. Zhou, D. Yang, and B. C. Low The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration J. Cell Sci., February 1, 2009; 122(3): 414 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kawai, Y. Iwamae, M. Yamaga, M. Kiyota, H. Ishii, H. Hirata, Y. Homma, and H. Yagisawa Focal adhesion-localization of START-GAP1/DLC1 is essential for cell motility and morphology. Genes Cells, February 1, 2009; 14(2): 227 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Holeiter, J. Heering, P. Erlmann, S. Schmid, R. Jahne, and M. A. Olayioye Deleted in Liver Cancer 1 Controls Cell Migration through a Dia1-Dependent Signaling Pathway Cancer Res., November 1, 2008; 68(21): 8743 - 8751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-C. Liao, Y.-P. Shih, and S. H. Lo Mutations in the Focal Adhesion Targeting Region of Deleted in Liver Cancer-1 Attenuate Their Expression and Function Cancer Res., October 1, 2008; 68(19): 7718 - 7722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lahoz and A. Hall DLC1: a significant GAP in the cancer genome Genes & Dev., July 1, 2008; 22(13): 1724 - 1730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Xue, A. Krasnitz, R. Lucito, R. Sordella, L. VanAelst, C. Cordon-Cardo, S. Singer, F. Kuehnel, M. Wigler, S. Powers, et al. DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma Genes & Dev., June 1, 2008; 22(11): 1439 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Hatch, Y. Gu, F. Y. Xu, J. Cizeau, S. Neumann, J.-S. Park, S. Loewen, and M. R.A. Mowat StARD13(Dlc-2) RhoGap Mediates Ceramide Activation of Phosphatidylglycerolphosphate Synthase and Drug Response in Chinese Hamster Ovary Cells Mol. Biol. Cell, March 1, 2008; 19(3): 1083 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Z. Pang, L.-X. Qin, N. Ren, Z.-Y. Hei, Q.-H. Ye, W.-D. Jia, B.-S. Sun, G.-L. Lin, D.-Y. Liu, Y.-K. Liu, et al. Loss of Heterozygosity at D8S298 Is a Predictor for Long-term Survival of Patients with Tumor-Node-Metastasis Stage I of Hepatocellular Carcinoma Clin. Cancer Res., December 15, 2007; 13(24): 7363 - 7369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fu, Y.-R. Qin, D. Xie, L. Hu, D. L. Kwong, G. Srivastava, S. W. Tsao, and X.-Y. Guan Characterization of a Novel Tumor-Suppressor Gene PLC{delta}1 at 3p22 in Esophageal Squamous Cell Carcinoma Cancer Res., November 15, 2007; 67(22): 10720 - 10726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Qian, G. Li, H. K. Asmussen, L. Asnaghi, W. C. Vass, R. Braverman, K. M. Yamada, N. C. Popescu, A. G. Papageorge, and D. R. Lowy Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities PNAS, May 22, 2007; 104(21): 9012 - 9017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Shang, S. Y. Moon, and Y. Zheng p200 RhoGAP Promotes Cell Proliferation by Mediating Cross-talk between Ras and Rho Signaling Pathways J. Biol. Chem., March 23, 2007; 282(12): 8801 - 8811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Liao, L. Si, R. W. deVere White, and S. H. Lo The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1 J. Cell Biol., January 1, 2007; 176(1): 43 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shi, J. Guo, D. J. Duff, F. Rahmatpanah, R. Chitima-Matsiga, M. Al-Kuhlani, K. H. Taylor, O. Sjahputera, M. Andreski, J. E. Wooldridge, et al. Discovery of novel epigenetic markers in non-Hodgkin's lymphoma Carcinogenesis, January 1, 2007; 28(1): 60 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. P. Yam, F. C. F. Ko, C.-Y. Chan, D.-Y. Jin, and I. O.-L. Ng Interaction of Deleted in Liver Cancer 1 with Tensin2 in Caveolae and Implications in Tumor Suppression. Cancer Res., September 1, 2006; 66(17): 8367 - 8372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y-F Song, R Xu, X-H Zhang, B-B Chen, Q Chen, Y-M Chen, and Y Xie High-frequency promoter hypermethylation of the deleted in liver cancer-1 gene in multiple myeloma J. Clin. Pathol., September 1, 2006; 59(9): 947 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Guan, X. Zhou, N. Soulitzis, D. A. Spandidos, and N. C. Popescu Aberrant Methylation and Deacetylation of Deleted in Liver Cancer-1 Gene in Prostate Cancer: Potential Clinical Applications Clin. Cancer Res., March 1, 2006; 12(5): 1412 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Hers, M. Wherlock, Y. Homma, H. Yagisawa, and J. M. Tavare Identification of p122RhoGAP (Deleted in Liver Cancer-1) Serine 322 as a Substrate for Protein Kinase B and Ribosomal S6 Kinase in Insulin-stimulated Cells J. Biol. Chem., February 24, 2006; 281(8): 4762 - 4770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yu, G. C. Tseng, Y. P. Yu, T. Gavel, J. Nelson, A. Wells, G. Michalopoulos, D. Kokkinakis, and J.-H. Luo CSR1 Suppresses Tumor Growth and Metastasis of Prostate Cancer Am. J. Pathol., February 1, 2006; 168(2): 597 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H.-Y. Leung, Y.-P. Ching, J. W. P. Yam, C.-M. Wong, T.-O. Yau, D.-Y. Jin, and I. O.-L. Ng Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity PNAS, October 18, 2005; 102(42): 15207 - 15212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Wong, J. W.-P. Yam, Y.-P. Ching, T.-O. Yau, T. H.-Y. Leung, D.-Y. Jin, and I. O.-L. Ng Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma Cancer Res., October 1, 2005; 65(19): 8861 - 8868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Goodison, J. Yuan, D. Sloan, R. Kim, C. Li, N. C. Popescu, and V. Urquidi The RhoGAP Protein DLC-1 Functions as a Metastasis Suppressor in Breast Cancer Cells Cancer Res., July 15, 2005; 65(14): 6042 - 6053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Alpy and C. Tomasetto Give lipids a START: the StAR-related lipid transfer (START) domain in mammals J. Cell Sci., July 1, 2005; 118(13): 2791 - 2801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-S. Jou, C.-S. Lee, Y.-H. Chang, C.-F. Hsiao, C.-F. Chen, C.-C. Chao, L. S.H. Wu, S.-H. Yeh, D.-S. Chen, and P.-J. Chen Clustering of Minimal Deleted Regions Reveals Distinct Genetic Pathways of Human Hepatocellular Carcinoma Cancer Res., May 1, 2004; 64(9): 3030 - 3036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamaga, M. Sekimata, M. Fujii, K. Kawai, H. Kamata, H. Hirata, Y. Homma, and H. Yagisawa A PLC{delta}1-binding protein, p122/RhoGAP, is localized in caveolin-enriched membrane domains and regulates caveolin internalization Genes Cells, January 1, 2004; 9(1): 25 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Wong, J. M.-F. Lee, Y.-P. Ching, D.-Y. Jin, and I. O.-l. Ng Genetic and Epigenetic Alterations of DLC-1 Gene in Hepatocellular Carcinoma Cancer Res., November 15, 2003; 63(22): 7646 - 7651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, L. Yang, Y. Luo, and Y. Zheng A Novel Strategy for Specifically Down-regulating Individual Rho GTPase Activity in Tumor Cells J. Biol. Chem., November 7, 2003; 278(45): 44617 - 44625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-P. Ching, C.-M. Wong, S.-F. Chan, T. H.-Y. Leung, D. C.-H. Ng, D.-Y. Jin, and I. O.-l. Ng Deleted in Liver Cancer (DLC) 2 Encodes a RhoGAP Protein with Growth Suppressor Function and Is Underexpressed in Hepatocellular Carcinoma J. Biol. Chem., March 14, 2003; 278(12): 10824 - 10830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Kim and X. W. Wang Gene expression profiling of preneoplastic liver disease and liver cancer: a new era for improved early detection and treatment of these deadly diseases? Carcinogenesis, March 1, 2003; 24(3): 363 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-Z. Yuan, X. Zhou, D. B. Zimonjic, M. E. Durkin, and N. C. Popescu Amplification and Overexpression of the EMS 1 Oncogene, a Possible Prognostic Marker, in Human Hepatocellular Carcinoma J. Mol. Diagn., February 1, 2003; 5(1): 48 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Casha, L. A. Davidson, P. Roberts, and R. U. Nair Familial angiosarcoma of the heart J. Thorac. Cardiovasc. Surg., August 1, 2002; 124(2): 392 - 394. [Full Text] [PDF]
|
|
|
|
|
|
I. O.-l. Ng, Z.-d. Liang, L. Cao, and T. K.-w. Lee DLC-1 Is Deleted in Primary Hepatocellular Carcinoma and Exerts Inhibitory Effects on the Proliferation of Hepatoma Cell Lines with Deleted DLC-1 Cancer Res., December 1, 2000; 60(23): 6581 - 6584. [Abstract] [Full Text]
|
|
|
|
|
|
Z.-Z. Zeng, S. Higashi, W. Kitayama, A. Denda, Y. Yan, K. Matsuo, Y. Konishi, H. Hiai, and K. Higashi Genetic Resistance to Chemical Carcinogen-induced Preneoplastic Hepatic Lesions in DRH Strain Rats Cancer Res., June 1, 2000; 60(11): 2876 - 2881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. H. Arbieva, K. Banerjee, S. Y. Kim, S. L. Edassery, V. S. Maniatis, S. K. Horrigan, and C. A. Westbrook High-Resolution Physical Map and Transcript Identification of a Prostate Cancer Deletion Interval on 8p22 Genome Res., February 1, 2000; 10(2): 244 - 257. [Abstract] [Full Text]
|
|
|
|
|
|
J.-P. Mira, V. Benard, J. Groffen, L. C. Sanders, and U. G. Knaus Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway PNAS, January 4, 2000; 97(1): 185 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-X. Qin, Z.-Y. Tang, J. S. T. Sham, Z.-C. Ma, S.-L. Ye, X.-D. Zhou, Z.-Q. Wu, J. M. Trent, and X.-Y. Guan The Association of Chromosome 8p Deletion and Tumor Metastasis in Human Hepatocellular Carcinoma Cancer Res., November 1, 1999; 59(22): 5662 - 5665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Knuutila, Y. Aalto, K. Autio, A.-M. Bjorkqvist, W.'e. El-Rifai, S. Hemmer, T. Huhta, E. Kettunen, S. Kiuru-Kuhlefelt, M. L. Larramendy, et al. DNA Copy Number Losses in Human Neoplasms Am. J. Pathol., September 1, 1999; 155(3): 683 - 694. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
