title: CHST11 gene expression and DNA methylation in breast cancer.
abstract: Our previously published data link P-selectin-reactive chondroitin sulfate structures on the surface of breast cancer cells to metastatic behavior of cells. We have shown that a particular sulfation pattern mediated by the expression of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness of human breast cancer cell lines. The present study was performed to evaluate the prognostic value of CHST11 expression and determine whether aberrant DNA methylation controls CHST11 expression in breast cancer. Publicly available datasets were used to examine the association of CHST11 expression to aggressiveness and progression of breast cancer. Methylation status was analyzed using bisulfite genomic sequencing. 5-aza-2'-deoxycytidine (5AzadC) was used for DNA demethylation. Reduced representation bisulfite sequencing was performed in the CpG island of CHST11 with a minimum coverage of 10. Quantitative real-time RT-PCR was employed to confirm the expression profile of CHST11 in breast cancer cell lines. Flow cytometry was also used to confirm the expression of the CHST11 product, chondroitin sulfate A (CS-A). The expression of CHST11 was significantly higher in basal-like and Her2-amplified cell lines compared to luminal cell lines. CHST11 was also highly expressed in cancer tissues compared to normal tissues and the expression levels were significantly associated with tumor progression. We observed very low levels of DNA methylation in a CpG island of CHST11 in basal-like cells but very high levels in the same region in luminal cells. Treatment of MCF7 cells, a luminal cell line with very low expression of CHST11, with 5AzadC increased the expression of CHST11 and its immediate product, CS-A, in a dose-dependent manner. These results suggest that CHST11 may play a direct role in progression of breast cancer and that its expression is controlled by DNA methylation. Therefore, in addition to CHST11 mRNA levels, the methylation status of this gene also has potential as a prognostic biomarker.
authors.affiliation: Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Damir
authors.initials: D
authors.lastname: Herman
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Leakey
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Behrens
authors.affiliation: Department of Medical Genetics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Aiwei
authors.initials: A
authors.lastname: Yao-Borengasser
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Cooney
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Fariba
authors.initials: F
authors.lastname: Jousheghany
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Bounleut
authors.initials: B
authors.lastname: Phanavanh
authors.affiliation: Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siegel
authors.affiliation: Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: A Mazin
authors.initials: AM
authors.lastname: Safar
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Soheila
authors.initials: S
authors.lastname: Korourian
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kieber-Emmons
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Behjatolah
authors.initials: B
authors.lastname: Monzavi-Karbassi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D011379:Prognosis; D015238:Sulfotransferases / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C411659:CHST11 protein, human; D015238:Sulfotransferases