Open AccessHigh expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers
Author(s) -
Shimada Mai,
Kitagawa Kyoko,
Dobashi Yoh,
Isobe Tomoyasu,
Hattori Takayuki,
Uchida Chiharu,
Abe Kenji,
Kotake Yojiro,
Oda Toshiaki,
Suzuki Hiroyuki,
Hashimoto Kenji,
Kitagawa Masatoshi
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01122.x
Subject(s) - ubiquitin ligase , downregulation and upregulation , cancer research , small interfering rna , ubiquitin , head and neck squamous cell carcinoma , immunohistochemistry , biology , cyclin d1 , cancer , cell culture , cell cycle , transfection , head and neck cancer , immunology , gene , genetics
Downregulation of the cyclin‐dependent kinase inhibitory protein p27 is frequently observed in various cancers due to enhancement of its degradation. We recently reported that p53‐inducible protein with RING‐H2 domain (Pirh2) is a novel ubiquitin ligase for p27, required for the ubiquitylation and consequent degradation of p27 protein. However, there is no reports about the involvement of Pirh2 in both p27 downregulation and pathogenesis in human cancers. In the present study, we investigated them using cultured cell lines and surgical specimens derived from human head and neck squamous cell carcinoma (HNSCC). Depletion of Pirh2 by short interfering RNA induced accumulation of p27 and inhibited the growth of cultured HNSCC cells. By immunohistochemical analysis in 57 cases of HNSCC specimens, higher levels of Pirh2 expression (labeling index ≥ 60%) were found in 61.4% of HNSCC in comparison with 0% of normal mucosa. In addition, 83.3% of HNSCC with lower p27 expression (labeling index < 20%) displayed high Pirh2 levels. Therefore, Pirh2 expression was inversely correlated with p27 expression. Finally, Pirh2 expression was well correlated with poor prognosis. These findings suggest that Pirh2 overexpression may have an important role in the development and maintenance of HNSCC at least partially through p27 degradation, and that Pirh2 may be a potential molecular target for human HNSCC. ( Cancer Sci 2009; 100: 866–872)