title: Histone H1 phosphorylation in breast cancer.
abstract: Breast cancer is the second leading cause of cancer-related deaths in women. The need for new clinical biomarkers in breast cancer is necessary to further predict prognosis and therapeutic response. In this article, the LC-MS histone H1 phosphorylation profiles were established for three distinct breast cancer cell lines. The results show that the extent of H1 phosphorylation can distinguish between the different cell lines. The histone H1 from the metastatic cell line, MDA-MB-231, was subjected to chemical derivitization and LC-MS/MS analysis. The results suggest that the phosphorylation at threonine 146 is found on both histone H1.2 and histone H1.4. Cell lines were then treated with an extracellular stimulus, estradiol or kinase inhibitor LY294002, to monitor changes in histone H1 phosphorylation. The data show that histone H1 phosphorylation can increase and decrease in response to extracellular stimuli. Finally, primary breast tissues were stained for the histone H1 phosphorylation at threonine 146. Variable staining patterns across tumor grades and subtypes were observed with pT146 labeling correlating with tumor grade. These results establish the potential for histone H1 phosphorylation at threonine 146 as a clinical biomarker in breast cancer.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, ‡Comprehensive Cancer Center, §Department of Chemistry & Biochemistry, ⊥Veterinary Biosciences, College of Veterinary Medicine, and ∥Department of Internal Medicine, Division of Hematology, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Harshman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hoover
authors.forename: Chengsi
authors.initials: C
authors.lastname: Huang
authors.forename: Owen E
authors.initials: OE
authors.lastname: Branson
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Chaney
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Cheney
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
authors.forename: Vicki H
authors.initials: VH
authors.lastname: Wysocki
authors.forename: Kay
authors.initials: K
authors.lastname: Huebner
authors.forename: Michael A
authors.initials: MA
authors.lastname: Freitas
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D013912:Threonine / Q000378:metabolism
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D004958:Estradiol; D006657:Histones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D020033:Protein Isoforms; D013912:Threonine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one