title: HET/SAF-B overexpression causes growth arrest and multinuclearity and is associated with aneuploidy in human breast cancer.
abstract: HET/SAF-B was originally cloned as a nuclear matrix protein that bound to matrix attachment regions and as a transcriptional repressor of the small heat shock protein hsp27. In addition, we have found recently that HET/SAF-B is also a corepressor of estrogen receptor activity. Estrogen receptor has a very well-described role in breast cancer, and aberrant expression of nuclear matrix and heat shock proteins has also been implicated in breast tumorigenesis. Therefore, we asked whether HET/SAF-B itself could be important in breast cancer. Toward this goal we examined its expression in breast cancer cell lines and asked whether HET/SAF-B can affect breast cancer cell proliferation. Finally, we studied HET/SAF-B expression in clinical breast cancer samples. HET/SAF-B protein and mRNA were detected at varying levels in all of the eight breast cancer cell lines examined. Using a number of different approaches to modulate the level of HET/SAF-B protein in the cell, we found that HET/SAF-B levels are inversely correlated with cell proliferation. In addition,transfection of HET/SAF-B fused to the green fluorescent protein led to the formation of multinucleated cells not observed in cells transfected with green fluorescent protein alone, suggesting that this effect is a direct result of HET/SAF-B overexpression. Western blot analysis of HET/SAF-B in 61 human breast tumors revealed widely varying levels of HET/SAF-B expression, with some tumors (16%) lacking any detectable HET/SAF-B. Statistical analysis showed that high HET/SAF-B expression in these tumors was associated with low S-phase fraction and with aneuploidy, consistent with our results from transfection experiments in tissue culture cells. We conclude that HET/SAF-B plays an important role in breast cancer, and we discuss possible mechanisms of the involvement of HET/SAF-B in cell proliferation and division.
authors.affiliation: Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Townson
authors.forename: T
authors.initials: T
authors.lastname: Sullivan
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
authors.forename: A V
authors.initials: AV
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D016475:3T3 Cells / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016466:CHO Cells / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D036961:Matrix Attachment Region Binding Proteins; D051379:Mice; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; C109132:SAFB protein, human; D049452:Green Fluorescent Proteins