title: CaSm-mediated cellular transformation is associated with altered gene expression and messenger RNA stability.
abstract: CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm encodes a 133 amino acid protein that contains two Sm motifs found in the common small nuclear RNA proteins and the LSm (like-Sm) family of proteins. Compared with normal human prostate tissue and primary prostate epithelial cells, some primary prostate tumors and prostate cancer-derived cell lines have elevated CaSm expression. Expression of antisense CaSm RNA in DU145 cells results in reduced CaSm protein levels and less transformed phenotype, measured by anchorage-independent growth in vitro and tumor formation in severe combined immunodeficient mice in vivo. Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins. Consistent with failure of antisense-treated cells to enter mitosis, microarray analysis identified altered expression of NEK2 and nucleophosmin/B23. Although the mechanisms by which CaSm contributes to neoplastic transformation and cellular proliferation are unknown, it has been shown that the yeast homologue (spb8/LSm1) of CaSm is required for 5' to 3' degradation of specific mRNAs. We provide data consistent with a similar role for CaSm in human cells, supporting the hypothesis that elevated CaSm expression observed in cancer leads to destabilization of multiple gene transcripts, contributing to the mutator phenotype of cancer cells.
authors: Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29403, USA.
authors: Melissa M
authors: MM
authors: Fraser
authors: Patricia M
authors: PM
authors: Watson
authors: Mostafa M
authors: MM
authors: Fraig
authors: Joseph R
authors: JR
authors: Kelley
authors: Peter S
authors: PS
authors: Nelson
authors: Alice M
authors: AM
authors: Boylan
authors: David J
authors: DJ
authors: Cole
authors: Dennis K
authors: DK
authors: Watson
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016195:G2 Phase / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins
chemical_list: C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C464824:LSM1 protein, human; D011518:Proto-Oncogene Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins