CaSm (LSm-1) Overexpression in Lung Cancer and Mesothelioma Is Required for Transformed Phenotypes
Mesothelioma
0301 basic medicine
0303 health sciences
Lung Neoplasms
RNA-Binding Proteins
Mice, SCID
3. Good health
Gene Expression Regulation, Neoplastic
Mice
03 medical and health sciences
Cell Transformation, Neoplastic
Phenotype
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Proto-Oncogene Proteins
Animals
Humans
RNA Interference
Neoplasm Transplantation
DOI:
10.1165/rcmb.2007-0205oc
Publication Date:
2008-01-25T02:24:59Z
AUTHORS (6)
ABSTRACT
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.
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