摘要：

We previously isolated and characterized a novel gene found to be elevated in pancreatic cancer and in several cancer-derived cell lines. This gene, CaSm (for Cancer-associated Sm-like), 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. By immunohistochemistry, tumor cells express higher levels of CaSm than adjacent normal tissue. In addition, human prostate cancer and mesothelioma derived cell lines have elevated CaSm expression when compared to normal tissue. These cell lines, transfected with and expressing antisense CaSm RNA demonstrate reduced CaSm protein and altered transformed phenotype, reducing their ability to form colonies in soft agar and tumors in SCID mice. This supports the model that elevated CaSm expression in epithelial tissue contributes to the transformed state. Additional data demonstrate that adenoviral delivery of antisense CaSm inhibits the growth of cancer cell lines by altering cell cycle progression. Cell lines expressing exogenous CaSm also exhibit characteristics consistent with a more transformed state, such as anchorage-independent colony formation and tumor growth in SCID mice. Although the mechanisms by which CaSm contributes to cellular proliferation and neoplastic transformation are unknown, CaSm (LSm1) exists as part of a seven membered ring structure that functions in mRNA degradation. We provide data demonstrating that down regulation of CaSm in human cancer cells increases mRNA stability and are examining the effect of CaSm expression on the relative abundance of other LSm proteins. Our collective data supports the hypothesis that elevated CaSm expression leads to destabilization of multiple gene transcripts, contributing to a mutator phenotype.

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