Enhancement of osteopontin expression in HepG2 cells by epidermal growth factor via phosphatidylinositol 3-kinase signaling pathway.
OBJECTIVE
Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. It is unclear how osteopontin is regulated in HepG2 cells. The aim of this study was to investigate the effect of epidermal growth factor on the expression of osteopontin in HepG2 cells, and to explore the signal transduction pathway mediated this expression.


METHODS
Osteopontin expression was detected by RNAase protection assay and Western blot. Wortmannin, a specific inhibitor of PI3K, was used to see if PI3K signal transduction was involved in the induction of osteopontin gene expression.


RESULTS
HepG2 cells constitutively expressed low levels of osteopontin. Treatment with epidermal growth factor increased osteopontin mRNA and protein level in a dose- and time-dependent manner. Application of wortmannin caused a dramatic reduction of epidermal growth factor-induced osteopontin expression.


CONCLUSIONS
Osteopontin gene expression can be induced by treatment of HepG2 cells with epidermal growth factor. Epidermal growth factor may regulate osteopontin gene expression through PI3K signaling pathway. Several potential targets in the pathway can be manipulated to block the synthesis of osteopontin and inhibit liver cancer metastasis.
Zhang
Guo-Xin
GX
Department of Gastroenterology, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. guoxinz2002@yahoo.com
Zhao
Zhi-Quan
ZQ
Wang
Hong-Di
HD
Hao
Bo
B
D000730:Androstadienes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012795:Sialoglycoproteins / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012795:Sialoglycoproteins; D000077191:Wortmannin; C506895:SPP1 protein, human