title: Expression of splicing factors in human ovarian cancer.
abstract: Alternative splicing represents an important nuclear mechanism in the post-transcriptional regulation of gene expression, which is frequently altered during tumorigenesis. Previously, we have described marked changes in alternative splicing of the CD44 gene in ovarian and breast cancer. In the latter one we described also a specific induction of splicing factors during tumor development. Now we have focussed our studies on the expression profiles of splicing factors, including classical SR proteins, Tra2 and YB-1 in physiological and malignant ovarian tissues by RT-PCR and Western blot analysis. We detected changed expression pattern with higher levels of phosphorylated 30 kDa SR proteins as well as relatively high concentrations of hyperphosphorylated Tra2 protein isoforms in ovarian cancer. RT-PCR analysis revealed a marked induction of SC35 and ASF/SF2 as well as mRNA levels in malignant ovarian tissue. These results suggest gene-specific alterations of expression rather than a general induction of the splicing machinery. Together with previously performed functional studies of CD44 splicing these findings implicate that altered expression profiles of SR proteins, Tra2beta and YB-1 might be responsible for the known changes of alternative CD44 splicing in ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Freiburg University Medical Center, D-79106 Freiburg, Germany.
authors.forename: D-C
authors.initials: DC
authors.lastname: Fischer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Noack
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Runnebaum
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Watermann
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Kieback
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D051840:Y-Box-Binding Protein 1
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D004268:DNA-Binding Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D000068103:Serine-Arginine Splicing Factors