Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is required for the transformed phenotype of murine pancreatic adenocarcinoma.
We have recently shown that the cancer-associated Sm-like protein (CaSm) is overexpressed in human pancreatic adenocarcinoma (PC). However, the role of CaSm in the process of neoplastic transformation remains unclear. To define further the role of CaSm in PC transformation, we have established a murine model based on the murine pancreatic cancer cell lines Panc02 and Panc03. CaSm is overexpressed in the aggressive Panc02 cells and expressed at much lower levels in the more indolent Panc03 cells. Up-regulation of CaSm in Panc03 cells increased in vitro proliferation and anchorage-independent growth and promoted subcutaneous tumor establishment and growth in syngeneic mice. Conversely, adenoviral down-regulation of CaSm in Panc02 led to significant inhibition of cellular proliferation and anchorage-independent growth in vitro and complete abolition of tumor growth and metastasis in vivo. Up-regulation of CaSm in NIH3T3 resulted in loss of contact inhibition and increased soft agar colony formation in vitro. The requirement for CaSm overexpression for neoplastic transformation confirms the concept that CaSm is a critical oncogene and potential target for molecular intervention. Furthermore, establishment of the murine clinically relevant model of pancreatic metastases provides a framework for the generation of preclinical data to support the development of novel molecular therapies targeting CaSm.
Yan
Yan
Y
Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 420, P O Box 250613, Charleston, SC 29425, USA.
Rubinchik
Semyon
S
Watson
Patricia M
PM
Kelley
Joseph R
JR
Fraser
Melissa M
MM
Wood
April L
AL
Dong
Jian-Yun
JY
Gillanders
William E
WE
Boylan
Alice M
AM
Watson
Dennis K
DK
Cole
David J
DJ
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D013997:Time Factors; D015854:Up-Regulation
C502231:Lsm1 protein, mouse; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins