| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Departments of Medical Oncology and Therapeutic Research,* Gastrointestinal Disease, Pathology, and Biostatistics, City of Hope National Medical Center, Duarte, California; Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; the Department of Pathology,¶ Ruijin Hospital, Shanghai Second Medical University, Shanghai, China; the Department of Surgery,|| Ruijin Hospital, Shanghai Second Medical University, Shanghai, China; the Department of Surgery,** St. Vincent Hospital, Los Angeles, California; and the Department of Pediatrics and Microbiology, University of Southern California, Los Angeles, California
In this study, we describe the growth arrest DNA damage-inducible gene 45ß (GADD45ß), whose expression was significantly down-regulated in the hepatocellular carcinoma (HCC) microarray study and confirmed by Northern blot analysis. The results suggested that expression of GADD45ß was decreased in human liver cancer cell lines HepG2 and Hep3B, but not in normal human embryonic liver cell line CL-48 or normal liver tissue. Histochemistry study and real-time PCR further confirmed that GADD45ß staining in HCC was significantly decreased when compared to surrounding non-neoplastic liver tissue. In further studies of multiple human cancer tissues, GADD45ß strongly stained tissues such as colon cancer, breast cancer, prostate cancer, squamous cell cancer, lymphoma, and leiomyosarcoma, suggesting that the decreased expression of GADD45ß is specific to HCC. Eighty-five cases of primary HCC were further examined by immunohistochemistry and statistical analyses demonstrated that HCC scored lower than matched non-neoplastic liver tissues consistently and significantly. No staining occurred in 12.94% of HCC cases (score = 0, n = 11); 42.35% had weak staining (score = 1, n = 36); 27.06% had moderate staining (score = 2, n = 23); and 17.65% had staining as strong as normal tissue (score = 3, n = 15). Overall, surrounding non-neoplastic liver tissue was highly positive for GADD45ß compared to adjacent neoplastic liver tissues (P < 0.01). We further observed that down-regulation of GADD45ß expression was strongly correlated with differentiation (P < 0.01) and high nuclear grade (P < 0.01). Moreover, we found that expression of GADD45ß was inversely correlated to the presence of mutant p53 in HCC tissue (P < 0.05). Thus, the results of our study suggest that GADD45ß, which is down-regulated in most cases of HCC, remains an ideal candidate for development as a molecular marker in the diagnosis of HCC and as a potential therapeutic target.
This article has been cited by other articles:
 |
|
 |
|
  W. Qiu, B. Zhou, P. G. Chu, F. Luh, and Y. Yen The Induction of Growth Arrest DNA Damage-Inducible Gene 45 {beta} in Human Hepatoma Cell Lines by S-Adenosylmethionine Am. J. Pathol., July 1, 2007; 171(1): 287 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ijiri, L. F. Zerbini, H. Peng, R. G. Correa, B. Lu, N. Walsh, Y. Zhao, N. Taniguchi, X.-L. Huang, H. Otu, et al. A Novel Role for GADD45{beta} as a Mediator of MMP-13 Gene Expression during Chondrocyte Terminal Differentiation J. Biol. Chem., November 18, 2005; 280(46): 38544 - 38555. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
