Expression of ROCK-1 in human pancreatic cancer: its down-regulation by morpholino oligo antisense can reduce the migration of pancreatic cancer cells in vitro.
BACKGROUND
Invasion and metastasis of cancer cells require cell motility and adhesion. The small GTPase Rho and one of its effector molecules ROCK regulate cytoskeleton and actomyosin contractility, and play a crucial role in cell adhesion and motility. Results of previous studies showed that the elevated activity of ROCK-1, one of the isomers of ROCK kinases, led to an increase in the activity of invasion and metastasis of cancer cell lines.


OBJECTIVE
To investigate the importance of ROCK-1 in cancer invasion and metastasis.


METHODS
We investigated the expression of ROCK-1 in two cancer cell lines and 31 human pancreatic tissues (21 pancreatic cancers [PC] and 10 histologically normal tissues) by immunoblotting and immunohistochemistry. We also examined by haptotaxis assay whether the migratory activity of PC cells could be suppressed by treatment with the morpholino antisense oligonucleotide in vitro.


RESULTS
The expression of ROCK-1 was found in 18 of 21 PC tissues (85.7%), but not in normal pancreatic tissues by immunoblotting and immunohistochemistry. Antisense oligo against ROCK-1 significantly inhibited the haptotaxis of Panc-1 in a dose-dependent manner, compared with the control oligo.


CONCLUSIONS
These results suggest that ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration.
Kaneko
Kenzo
K
Department of Gastroenterology, Division of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. kkaneko@int3.med.tohoku.ac.jp
Satoh
Kennichi
K
Masamune
Atsushi
A
Satoh
Akihiko
A
Shimosegawa
Tooru
T
D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases