Ribozyme targeting of HER-2 inhibits pancreatic cancer cell growth in vivo.
We have analysed HER-2 expression and function in pancreatic cancer cells to determine whether HER-2 has a rate-limiting role for pancreatic cancer cell growth in vitro and in vivo. To specifically assess HER-2 function, we used HER-2-targeted ribozymes expressed under the control of the tet-off promoter system. Six out of 11 human pancreatic cancer cell lines expressed all four epidermal growth factor (EGF)-receptor family members (HER-1 (EGF-R), HER-2, HER-3, and HER-4), including Panc89 cells. Expression of the ribozymes quenched endogenous HER-2 mRNA levels in Panc89 cells by approximately 40-60% which was reflected by a 40-50% reduction of the HER-2 surface glycoprotein. HER-2 depletion inhibited the in vitro proliferation rate by approximately 40% and decreased in vivo tumour growth by approximately 60% (P<0.05). Our study demonstrates for the first time a rate-limiting role for HER-2 in pancreatic cancer cell proliferation and suggests HER-2 targeting as a potential approach in pancreatic cancer therapy.
Thybusch-Bernhardt
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A
Department of Surgery, University Hospital Kiel, 24105 Kiel, Germany.
Aigner
A
A
Beckmann
S
S
Czubayko
F
F
Juhl
H
H
D000818:Animals; D002455:Cell Division; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D016337:RNA, Catalytic / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013752:Tetracycline / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016337:RNA, Catalytic; D018719:Erb-b2 Receptor Tyrosine Kinases; D013752:Tetracycline; D015534:Trans-Activators