Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization.
Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of this study was to identify unique oncogenes that are differentially expressed in human cancers and characterize their functions in tumorigenesis. To discover new putative oncogenes, the differential display RT-PCR method was applied using normal cervical tissues, cervical cancer cell lines, cervical cancer tissues, and metastatic tissues. We identified a new human cervical cancer oncogene HCCR-2 that was overexpressed in various human tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon, and uterine cervix. Ectopic expression of HCCR-2 resulted in direct tumorigenic conversions of NIH/3T3 and Rat1 fibroblasts. Nude mice injected with NIH/3T3 cells stably transfected with HCCR-2 formed tumors in 4 weeks. The resultant tumors display characteristics of an epithelial carcinoma. In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of p53-induced p21(WAF1), MDM2, and bax. These results indicate that HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor.
Ko
Jesang
J
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
Lee
Young Han
YH
Hwang
Seung Yong
SY
Lee
Youn Soo
YS
Shin
Seung Min
SM
Hwang
Jae Hoon
JH
Kim
Jin
J
Kim
Yong Wook
YW
Jang
Sung-Wuk
SW
Ryoo
Zae Young
ZY
Kim
In-Kyung
IK
Namkoong
Sung Eun
SE
Kim
Jin Woo
JW
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008074:Lipoproteins / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D010770:Phosphotransferases; D011518:Proto-Oncogene Proteins; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; C492236:Cdk5r1 protein, mouse; C492235:Cdk5r1 protein, rat; C476732:LETMD1 protein, human; D008074:Lipoproteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D008156:Luciferases; D010770:Phosphotransferases