Joanne Jeou-Yuan Chen (張久瑗兼任副教授)
PhD. University of Minnesota
Gastric cancer (GC) is highly prevalent. To systematically dissect the pathways that are involved in the initiation and progression of this disease, various approaches of representational difference analysis (RDA) have been taken to isolate GC associated genes. By genomic RDA, chromosomal instability and microsatellite instability have been determined in GC at a genome-wide level. A subset of GC was characteristic of high microsatellite instability as the result of mutations in mismatch repair genes. In other GCs, distinct patterns of chromosomal instability and DNA copy number changes are tightly associated with specific clinicopathologic features. Candidate gene approach is underway to further explore the regions that may harbor candidate oncogenes or tumor suppressor genes dominating the pathogenic development of specific subtypes of GC. By various mRNA RDA, we have identified two thousands more genes that are differentially expressed in GC. A GC gene chip based on the cDNA of these genes was established and microarray hybridization was performed followed by cluster analyses to identify candidate genes associated with the pathogenic development of GC of specific histopathologic subtypes and stages. Genes that are involved in various pathways regulating cell proliferation or survival are focused and the potential usage of them as molecular markers for GC patients is evaluated. By proteomics, we are using humoral antibodies elicited in the sera of GC patients as reagents to isolate tumor antigens, with the hope to identify overexpressed candidate genes that may play important roles in gastric tumorigenesis. The goals of these studies are to provide a broad scope of the genetic events that are involved in the pathogenic development of gastric adenocarcinoma, with the hope to establish better choices of useful diagnostic and prognostic markers, and in the long run, to provide us the common denominator for understanding, treating, and preventing this disease.
Wu, C.-W., Lin, Y.-Y., Chen. G.-D., Chi, C.-W. and Chen, J.-Y.* Serum anti-p53 antibodies in gastric adenocarcinoma patients are associated with poor prognosis, nodal involvement and poorly differentiated nuclear grade. Brit. J. Cancer 80: 483-488, 1999.
Lo, P.-K., Chen, J.-Y., Yang, Y., Chen, B.-F., Tang, P.-P. and Wang, F.-F.* Identification of a novel p53 target gene DDA3. Oncogene 18: 7765-7774, 1999.
Wu, C.-W., Chen, G.-D., Chi, C.-W., Lee, A. F.-Y., Lo, S.-S. and Chen, J.-Y. A genome-wide study of microsatellite instability in advanced gastric cancer. Cancer 92: 92-101, 2001.
Hsu, L.-S., Chen, G.-D., Lee, L.-H., Chi, C.-W., Cheng, J.-F. and Chen, J.-Y.* Human Ca2+/calmodulin-dependent protein kinase kinase b gene encodes multiple isoforms that display distinct kinase activity. J. Biol. Chem. 276: 31113-31123, 2001.
Lo, P.-K., Chen, J.-Y., Tang, P.-P., Lin, J., Lin, C.-H., Su, L.-T., Wu, C.-H., Chen, T.-L., Yang, Y. and Wang, F.-F.* Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53. J. Biol. Chem. 276: 37186-37193, 2001.
Wu, C.-W., Chen, G.-D., Fann, C. S.-J., Lee, A. F.-Y., Chi, C.-W., Liu, J. M., Weier, U. and Chen, J.-Y.* Clinical implications of chromosomal abnormalities in gastric adenocarcinomas. Genes, Chromosomes and Cancer. 35:219-231, 2002.
Huang, C.-J. and Chen, J.-Y.* Identification of Additional IE2-p86-responsive Cis-repressiive Sequences within the Human Cytomegalovirus Major Immediate Early Promoter. J. Biomed. Sci. 9:460-470, 2002.
Fann, C. S.-J., Chen, J.-Y.*, Wu, C.-W., and Chi, C.-W. Regarding clinical implications of chromosomal abnormalities in gastric adenocarcinomas. Genes, Chromosomes, and Cancer 38:204-206, 2003.
Kao, C.-F., Chen, S.-Y., Chen, J.-Y., and Lee, Y.-H. W.* Modulation of p53 Transcription Regulatory Activity and Posttranslational Modification by Hepatitis C Virus Core Protein. Oncogene 23: 2472-83, 2004.
Sue, S.-C., Chen, J.-Y., and Huang, T.-H.* Sequence Specific 1H, 13C and 15N Resonance Assignments of the Hath-domain of Human Hepatoma-derived Growth Factor. J. Biomolecular NMR. 29:95-96, 2004.
Liu, C.-A., Wang, M.-J., Chi, C.-W., Wu, C.-W., and Chen, J.-Y.* Overexpression of Rho Effector Rhotekin Confers Increased Survival in Gastric Adenocarcinoma. J. Biomed. Sci. (In press), 2004.
Liu, C.-A., Wang, M.-J., Chi, C.-W., Wu, C.-W., and Chen, J.-Y.* Rho/Rhotekin-mediated NF-kB Activation Confers Resistance to Apoptosis. Oncogene (In press).