Epidermal growth factor receptor vIII enhances tumorigenicity and resistance to 5-fluorouracil in human hepatocellular carcinoma.
We investigated whether EGFRvIII contributes to tumorigenicity and resistance to 5-FU in HCC cell lines. Our results show that several HCC cell lines have EGFRvIII expression. EGFRvIII-positive HCC cells grew more rapidly and had a lower sensitivity to 5-FU than EGFRvIII-negative HCC cells. For further analysis of the biological characteristics of EGFRvIII, an EGFRvIII or EGFR expression cassette was introduced into the HCC cell line, Huh-7. Compared with Huh-7 cells and Huh7-EGFR cells, Huh7-EGFRvIII not only exhibit significantly increase of cell growth in vitro and in vivo but also show enhanced migration in vitro. Furthermore, 5-FU has significantly lower inhibition effect on Huh7-EGFRvIII cells then on both Huh-7 and Huh7-EGFR cells in vitro and in vivo. Collectively, these results demonstrate that EGFRvIII plays a pivotal role in tumorigenicity and enhanced 5-FU resistance of HCC.
Wang
Huamao
H
Medical School of Fudan University, Shanghai, China.
Jiang
Hua
H
Zhou
Min
M
Xu
Zhibing
Z
Liu
Shiguo
S
Shi
Bizhi
B
Yao
Xiao
X
Yao
Ming
M
Gu
JianRen
J
Li
Zonghai
Z
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human; D066246:ErbB Receptors; D005472:Fluorouracil