title: Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is required for the transformed phenotype of murine pancreatic adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 420, P O Box 250613, Charleston, SC 29425, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Semyon
authors.initials: S
authors.lastname: Rubinchik
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Watson
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Kelley
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Fraser
authors.forename: April L
authors.initials: AL
authors.lastname: Wood
authors.forename: Jian-Yun
authors.initials: JY
authors.lastname: Dong
authors.forename: William E
authors.initials: WE
authors.lastname: Gillanders
authors.forename: Alice M
authors.initials: AM
authors.lastname: Boylan
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Watson
authors.forename: David J
authors.initials: DJ
authors.lastname: Cole
mesh_terms: 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
chemical_list: C502231:Lsm1 protein, mouse; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins