Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas.
Functional inactivation of tumor susceptibility gene tsg101 leads to cellular transformation and tumorigenesis in mice. While human TSG101 is located in a region where frequent loss of heterozygosity can be detected in a variety of cancers, no genomic deletion in TSG101 gene has been reported, casting a doubt on the role of TSG101 as a classical tumor suppressor. Some studies have revealed that TSG101 is a frequent target of splicing defects, which correlate with cellular stress and p53 status. Furthermore, recent reports have identified TSG101 as a part of the MDM2/p53 regulatory circuitry, a well-recognized circuitry that upon deregulation results in tumorigenesis. Interestingly, overexpression of tsg101 from an adventitious promoter also leads to neoplastic transformation. On the basis of this information, we have analysed TSG101 gene expression in 20 human papillary thyroid carcinomas (PTCs) by immunohistochemistry and demonstrated that the overexpression of TSG101 protein is closely associated with human PTCs. Further sequence analysis reveals no mutation in cDNA region encoding steadiness box in these PTC specimens, indicating that the upregulation of TSG101 protein is not caused by the alteration of this region. In situ hybridization analysis confirms that overexpression of TSG101 also occurs at the transcriptional level. In addition, semi-quantitative RT-PCR and subsequent Southern hybridization verify that the amounts of TSG101 transcripts are indeed lower in three normal thyroid tissues than in PTC specimens. Here we report the upregulation of TSG101 expression in PTC cells, providing the first evidence of the association of TSG101 overexpression with human tumors and suggesting that upregulation of TSG101 steady-state level might play a role in mediating tumorigenesis of human PTC.
Liu
Rue-Tsuan
RT
Division of Metabolism, Chang Gung Memorial Hospital, Kaohsiung, Taiwan 833, Republic of China.
Huang
Chao-Cheng
CC
You
Huey-Ling
HL
Chou
Fong-Fu
FF
Hu
Chih-Chi Andrew
CC
Chao
Fang-Ping
FP
Chen
Ching-Mei
CM
Cheng
Jiin-Tsuey
JT
D000918:Antibody Specificity; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009154:Mutation; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015533:Transcriptional Activation; D015854:Up-Regulation; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D012334:RNA, Neoplasm; D014157:Transcription Factors; D000099177:Tsg101 Protein