HIF1α in Tumorigenesis of Adenoid Cystic Carcinoma.
Tumor hypoxia induces hypoxia-inducible factor-1α (HIF1α), which can influence tumorigenesis and metastasis. We evaluated the expression of HIF1α and the effect of HIF1α inhibitors in adenoid cystic carcinoma (ACC).



HIF1α expression was demonstrated in ACC cell lines (ACC2 and ACCM). The effect of HIF1α inhibitors was evaluated. A systemic metastasis model was developed. The number of metastatic pulmonary nodules were analyzed.



The ACCM cell line demonstrated greater HIF1α expression and invasion than ACC2. The expression of HIF1α and invasion of ACC cells were blocked by HIF1α siRNA. HIF1α inhibitors 17-N-allylamino-17-demethoxygeldanamycin (17AAG) and echinomycin inhibited cell invasion. 17AAG inhibited metastasis in the animal model, although not statistically significantly.



HIF1α siRNA and 17AAG and echinomycin blocked invasion by ACC2 and ACCM cells. 17AAG exhibited therapeutic potential for inhibition of metastasis. Our results provide positive evidence that HIF1α is a promising research pathway for therapy of ACC.
Department of Otorhinolaryngology-Head and Neck Surgery, Ilsan Hospital, Dongguk University, Goyang, Republic of Korea.
Yun-Sung
YS
Lim
Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University School of Medicine, Busan, Republic of Korea.
Wonjae
W
Cha
Department of Otorhinolaryngology-Head and Neck Surgery, Ilsong Memorial Institute of Head and Neck Cancer, Hallym University, College of Medicine, Seoul, Republic of Korea.
Min-Woo
MW
Park
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Woo-Jin
WJ
Jeong
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea ahnsh30@snu.ac.kr.
Soon-Hyun
SH
Ahn
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D015153:Blotting, Western; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004448:Echinomycin / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control / Q000556:secondary; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D016227:Benzoquinones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047029:Lactams, Macrocyclic; C112765:tanespimycin; D004448:Echinomycin
HIF1α; adenoid cystic carcinoma; animal model; invasion; metastasis