Inhibition of pancreatic cancer cell growth in vivo using a tetracycline-inducible cyclin D1 antisense expression system.
OBJECTIVE
Cyclin D1 is important for pancreatic cancer growth. Our aim was to determine the effects of cyclin D1 inhibition on the growth of established pancreatic tumors.


METHODS
PANC-1 cells harboring cyclin D1 antisense cDNA in a tetracycline-inducible vector system were prepared. The effects of cyclin D1 inhibition after tumor development were characterized in a mouse model.


RESULTS
In vitro removal of tetracycline induced cyclin D1 antisense cDNA expression and inhibited cyclin D1 expression and cyclin D1-associated kinase activity as well as anchorage-dependent and -independent growth. After establishment of xenograft tumors in the presence of tetracycline (2 mg/mL) in the drinking water, animals were assigned to either control (tetracycline remained in the drinking water) or to the group without tetracycline for which tetracycline was removed from the drinking water. Tumor growth was significantly inhibited after removal of tetracycline. Microscopic analysis revealed that the area of central necrosis was significantly increased in the group without tetracycline paralleled by a reduction of the vital peripheral area of proliferating cells.


CONCLUSIONS
Our results confirmed that cyclin D1 plays an important role in the growth of pancreatic cancer cells and may be an attractive molecular target for the treatment of human pancreatic cancer.
Department of General, Visceral, and Transplantation Surgery, University of Ulm, Ulm, Germany.
Jian Cheng
JC
Wang
Matthias
M
Thiere
Doris
D
Henne-Bruns
Uwe
U
Knippschild
Marko
M
Kornmann
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D016373:DNA, Antisense / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013752:Tetracycline / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
C530104:CCND1 protein, human; D016373:DNA, Antisense; D019938:Cyclin D1; D013752:Tetracycline