title: Aurora B expression and histone variant H1.4S27 phosphorylation are no longer coordinated during metaphase in aneuploid colorectal carcinomas.
abstract: Experimental model systems identified phosphorylation of linker histone variant H1.4 at Ser 27 (H1.4S27p) as a novel mitotic mark set by Aurora B kinase. Here, we examined expression of Aurora B and H1.4S27p in colorectal carcinoma (CRC) cell lines (HCT116, DLD1, Caco-2, HT29) and tissue specimens (n = 36), in relation to microsatellite instability (MSI) status and ploidy. In vitro, Aurora B (pro-/meta-/anaphase) and H1.4S27p (pro-/metaphase) were localized in mitotic figures. The proportion of labeled mitoses was significantly different between cell lines for Aurora B (p = 0.019) but not for H1.4S27p (p = 0.879). For Aurora B, these differences were not associated with an altered Aurora B gene copy number (FISH) or messenger RNA (mRNA) expression level (qRT-PCR). Moreover, Aurora B expression and H1.4S27 phosphorylation were no longer coordinated during metaphase in aneuploid HT29 cells (p = 0.039). In CRCs, immunoreactivity for Aurora B or H1.4S27p did not correlate with T- or N-stage, grade, or MSI status. However, metaphase labeling of H1.4S27p was significantly higher in diploid than in aneuploid CRCs (p = 0.011). Aurora B was significantly correlated with H1.4S27p-positive metaphases in MSI (p = 0.010) or diploid (p = 0.003) CRCs. Finally, combined classification of MSI status and ploidy revealed a significant positive correlation of Aurora B with H1.4S27p in metaphases of diploid/MSI (p = 0.010) and diploid/microsatellite-stable (MSS; p = 0.031) but not of aneuploid/MSS (p = 0.458) CRCs. The present study underlines the functional link of Aurora B expression and H1.4S27p during specific phases of mitosis in diploid and/or MSI-positive CRCs in vitro and in situ. Importantly, the study shows that the coordination between Aurora B expression and phosphorylation of H1.4 at Ser 27 is lost in cycling aneuploid CRC cells.
authors: Department of Pathology, University Medical Center, Breisacherstrasse 115A, 79106, Freiburg, Germany.
authors: Fahima
authors: F
authors: Sijare
authors: Anna-Lena
authors: AL
authors: Geißler
authors: Christiane D
authors: CD
authors: Fichter
authors: Sonja P
authors: SP
authors: Hergeth
authors: Lioudmila
authors: L
authors: Bogatyreva
authors: Dieter
authors: D
authors: Hauschke
authors: Robert
authors: R
authors: Schneider
authors: Martin
authors: M
authors: Werner
authors: Silke
authors: S
authors: Lassmann
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics*; D000782:Aneuploidy; D064107:Aurora Kinase B / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008677:Metaphase; D053842:Microsatellite Instability; D010766:Phosphorylation
chemical_list: D006657:Histones; C576921:AURKB protein, human; D064107:Aurora Kinase B