Ubiquitin-conjugating enzyme UBE2Q2 suppresses cell proliferation and is down-regulated in recurrent head and neck cancer.
The ubiquitin-proteasome system has a crucial role in maintaining and regulating cellular homeostasis including carcinogenesis. UBE2Q2, also designated Ubci, is one of the ubiquitin-conjugating enzymes (E2), and it has been reported that mRNA of UBE2Q2 is highly expressed in human head and neck squamous cell carcinoma, particularly hypopharyngeal carcinoma. However, the involvement of UBE2Q2 in carcinogenesis has not been fully elucidated. Most cases of head and neck carcinoma are treated with cis-diamminedichloroplatinum (II; CDDP) or docetaxel, which are the most effective chemotherapeutic agents against squamous cell carcinomas. Nevertheless, some head and neck cancers develop resistance to these drugs, although the causes and mechanisms remain unknown. In this study, we found high expression levels of UBE2Q2 in human head and neck carcinoma cell lines and cancer tissues by using an anti-UBE2Q2 antibody at the protein level. We also found that the expression level of UBE2Q2 is decreased in cell lines and cancer tissues that have resistance to CDDP or docetaxel and in cancer tissues treated with CDDP or docetaxel. Furthermore, we found that overexpression of UBE2Q2 affects cell proliferation and anchorage-independent cell growth. These findings suggest that UBE2Q2 is a novel oncosuppressor that inhibits tumor growth and is related to the resistance to anticarcinoma agents and that UBE2Q2 likely functions as a novel diagnostic tool and a potentially therapeutic target for head and neck squamous cell carcinoma.
Maeda
Hiroyuki
H
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Miyajima
Naoto
N
Kano
Satoshi
S
Tsukiyama
Tadasuke
T
Okumura
Fumihiko
F
Fukuda
Satoshi
S
Hatakeyama
Shigetsugu
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002522:Chlorocebus aethiops; D002945:Cisplatin / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D000077143:Docetaxel; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D041681:NIH 3T3 Cells; D015398:Signal Transduction; D043823:Taxoids / Q000494:pharmacology; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis* / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D043823:Taxoids; D000077143:Docetaxel; C507338:UBE2Q2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D019061:src-Family Kinases; D002945:Cisplatin