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CaSm (LSm-1) Overexpression in Lung Cancer and Mesothelioma Is Required for Transformed Phenotypes

¹ Departments of Medicine, Division of Pulmonary and Critical Care Medicine, ² Pathology and Laboratory Medicine, ³ Surgery, and ⁴ Biochemistry and Molecular Biology, and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina

Correspondence and requests for reprints should be addressed to Patricia M. Watson, PhD, Hollings Cancer Center, Room 333, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425. E-mail: watsonpm{at}musc.edu.

CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines. It encodes a 133–amino acid protein that contains two Sm motifs found in the common snRNP proteins and the LSm (like-Sm) family of proteins. Lung tumors and mesotheliomas express high levels of CaSm mRNA and protein compared with adjacent nontumor and normal lung tissue, measured by immunohistochemistry, qRT-PCR, and Western blot analyses. In addition, several human lung cancer– and mesothelioma-derived cell lines have elevated CaSm expression. Two cell lines, transfected with and expressing antisense CaSm RNA, demonstrate altered transformed phenotypes, reducing their ability to form colonies in soft agar and tumors in SCID mice. Furthermore, RNAi-mediated reduction of CaSm RNA and protein is associated with inhibition of cellular growth. These data support the model that elevated CaSm expression in epithelial tissue contributes to the transformed state. Cell lines expressing exogenous CaSm also exhibit transformed characteristics, including increased anchorage-independent colony formation and tumor growth. Thus, the results of loss of function and gain of function studies presented both indicate that CaSm functions as an oncogene in the promotion of cellular transformation and cancer progression.

Key Words: CaSm • Sm protein • transformation • lung cancer • mesothelioma

CLINICAL RELEVANCE We demonstrate that CaSm is necessary for transformation by loss-of-function and gain-of-function experiments. Also, these studies suggest that alterations in the mRNA degradation pathway may be a mechanism for the genetic disruptions seen in cancer.