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Williams, Cecilia, ProfessorORCID iD iconorcid.org/0000-0002-0602-2062
Publications (10 of 36) Show all publications
Katona, B., Ibrahim, A., Sundberg, M. & Williams, C. (2019). Antibody Validation Strategy for Nuclear Receptors.. Methods in Molecular Biology, 1966, 79-99
Open this publication in new window or tab >>Antibody Validation Strategy for Nuclear Receptors.
2019 (English)In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1966, p. 79-99Article in journal (Refereed) Published
Abstract [en]

Antibodies are invaluable biological tools that we can use to detect the presence, location, or alteration of nuclear receptors. However, antibodies frequently cross-react with other proteins and their performance can vary from batch to batch, from application to application and from lab to lab. When each lot of antibody is not thoroughly validated for each assay, each sample type, and each lab and user, antibody-based assays can lead to flawed interpretations and reproducibility problems. In this chapter, we describe a scheme for thorough antibody validation, suitable for nuclear receptors. The method is based on using highly characterized positive and negative controls assembled into a validation tissue microarray (TMA). Through correlation of immunohistochemical staining (IHC) and mRNA levels over multiple tissues, use of current public databases, and assessment of binding to intended and nonintended targets using western blotting (WB), immunoprecipitation (IP), and mass spectrometry (MS), we describe a path for thoroughly validation of antibodies.

Keywords
Antibody, Estrogen receptor, Immunohistochemistry, Immunoprecipitation, Mass spectrometry, Nuclear receptors, RNA-Seq, Tissue microarray, Validation, Western blotting
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:kth:diva-257973 (URN)10.1007/978-1-4939-9195-2_7 (DOI)31041740 (PubMedID)2-s2.0-85065404524 (Scopus ID)
Note

QC 20190917

Available from: 2019-09-09 Created: 2019-09-09 Last updated: 2019-09-17Bibliographically approved
Ibrahim, A., Hugerth, L. W., Hases, L., Saxena, A., Seifert, M., Thomas, Q. A., . . . Williams, C. (2019). Colitis-induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity. International Journal of Cancer, 144(12), 3086-3098
Open this publication in new window or tab >>Colitis-induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 12, p. 3086-3098Article in journal (Refereed) Published
Abstract [en]

Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone-replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine-specific deletion of ERβ (ERβKOVil ) were generated using the Cre-LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water. The microbiota population were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples (N = 39). Differences in the microbiota due to AOM/DSS and absence of ERβ were identified through bioinformatic analyses of the 16S-Seq data, and the distribution of bacterial species was corroborated using qPCR. We demonstrate that colitis-induced CRC reduced the gut microbiota diversity and that loss of ERβ enhanced this process. Further, the Bacteroidetes genus Prevotellaceae_UCG_001 was overrepresented in AOM/DSS mice compared to untreated controls (3.5-fold, p = 0.004), and this was enhanced in females and in ERβKOVil mice. Overall, AOM/DSS enriched for microbiota impacting immune system diseases and metabolic functions, and lack of ERβ in combination with AOM/DSS enriched for microbiota impacting carbohydrate metabolism and cell motility, while reducing those impacting the endocrine system. Our data support that intestinal ERβ contributes to a more favorable microbiome that could attenuate CRC development.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
AOM/DSS model, colitis-associated colon cancer, estrogen receptor beta, microbiota
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:kth:diva-244808 (URN)10.1002/ijc.32037 (DOI)000466449100019 ()30515752 (PubMedID)2-s2.0-85059884325 (Scopus ID)
Note

QC 20190304

Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-05-20Bibliographically approved
Zheng, D., Trynda, J., Williams, C., Vold, J. A., Nguyen, J. H., Harnois, D. M., . . . Li, Z. (2019). Sexual dimorphism in the incidence of human cancers. BMC Cancer, 19(1), Article ID 684.
Open this publication in new window or tab >>Sexual dimorphism in the incidence of human cancers
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2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, no 1, article id 684Article in journal (Refereed) Published
Abstract [en]

BackgroundSex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers.MethodsWe analyzed four sets of cancer incidence data from the SEER (USA, 1975-2015), from the Cancer Registry at Mayo Clinic (1970-2015), from Sweden (1970-2015), and from the World Cancer Report in 2012.ResultsWe found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant.ConclusionsSexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Sexual dimorphism, Cancer incidence, Human cancers
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-255560 (URN)10.1186/s12885-019-5902-z (DOI)000475527400003 ()31299933 (PubMedID)2-s2.0-85068997038 (Scopus ID)
Note

QC 20190805

Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-05Bibliographically approved
Danielsson, F., Fasterius, E., Sullivan, D., Hases, L., Sanli, K., Zhang, C., . . . Lundberg, E. (2018). Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia. OncoTarget, 9(28), 19730-19744
Open this publication in new window or tab >>Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 28, p. 19730-19744Article in journal (Refereed) Published
Abstract [en]

In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing their surrounding vasculature network. Transformed cancer cells are known to exhibit phenotypic alterations, enabling continuous proliferation despite a limited oxygen supply. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines of the BJ model responded strikingly different to hypoxia. Besides corroborating many of the known responses to hypoxia, we demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response.

Place, publisher, year, edition, pages
Impact Journals LLC, 2018
Keywords
Hypoxia, Malignant transformation, Transcriptomics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-227616 (URN)10.18632/oncotarget.24808 (DOI)2-s2.0-85045315705 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180522

Available from: 2018-05-22 Created: 2018-05-22 Last updated: 2019-04-26Bibliographically approved
Andersson, S., Sundberg, M., Pristovsek, N., Ibrahim, A., Jonsson, P., Katona, B., . . . Asplund, A. (2017). Insufficient antibody validation challenges oestrogen receptor beta research. Nature Communications, 8, Article ID 15840.
Open this publication in new window or tab >>Insufficient antibody validation challenges oestrogen receptor beta research
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 15840Article in journal (Refereed) Published
Abstract [en]

The discovery of oestrogen receptor beta (ER beta/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ER alpha (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ER beta antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ER beta in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ER beta protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies can lead an exciting field astray.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-210349 (URN)10.1038/ncomms15840 (DOI)000403317200001 ()2-s2.0-85020892431 (Scopus ID)
Note

QC 20170704

Available from: 2017-07-04 Created: 2017-07-04 Last updated: 2019-03-11Bibliographically approved
Williams, C., DiLeo, A., Niv, Y. & Gustafsson, J.-A. (2016). Estrogen receptor beta as target for colorectal cancer prevention. Cancer Letters, 372(1), 48-56
Open this publication in new window or tab >>Estrogen receptor beta as target for colorectal cancer prevention
2016 (English)In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 372, no 1, p. 48-56Article, review/survey (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ER beta/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ER beta selective agonists, can activate or upregulate ER beta in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ER beta may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Colorectal cancer, Estrogen, Estrogen receptor beta, Phytoestrogens, Prevention, Gene expression
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-184022 (URN)10.1016/j.canlet.2015.12.009 (DOI)000370832600005 ()26708506 (PubMedID)2-s2.0-84958213395 (Scopus ID)
Note

QC 20160324

Available from: 2016-03-24 Created: 2016-03-22 Last updated: 2017-11-30Bibliographically approved
Katchy, A. & Williams, C. (2016). Expression Profiles of Estrogen-Regulated MicroRNAs in Breast Cancer Cells. In: Kathleen M. Eyster (Ed.), Methods in Molecular Biology: The Estrogen Receptors. Springer, 1366
Open this publication in new window or tab >>Expression Profiles of Estrogen-Regulated MicroRNAs in Breast Cancer Cells
2016 (English)In: Methods in Molecular Biology: The Estrogen Receptors / [ed] Kathleen M. Eyster, Springer, 2016, Vol. 1366Chapter in book (Other academic)
Abstract [en]

Molecular signaling through both estrogen and microRNAs are critical for breast cancer development and growth. The activity of estrogen is mediated by transcription factors, the estrogen receptors. Here we describe a method for robust characterization of estrogen-regulated microRNA profiles. The method details how to prepare cells for optimal estrogen response, directions for estrogen treatment, RNA extraction, microRNA large-scale profiling, and subsequent confirmations.

Place, publisher, year, edition, pages
Springer, 2016
Keywords
Receptor Tyrosine Kinase, Mammary Epithelial-Cells, Activated Protein-Kinase, Mesenchymal Transition, Posttranscriptional Regulation, Gene-Expression, Stem-Cells, Microrna, Progression, Family
National Category
Natural Sciences Biological Sciences Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-178111 (URN)10.1007/978-1-4939-3127-9_30 (DOI)26585151 (PubMedID)2-s2.0-84947781743 (Scopus ID)
Note

QC 20151214

Available from: 2015-12-07 Created: 2015-12-07 Last updated: 2018-01-10Bibliographically approved
Reins, R. Y., Mesmar, F., Williams, C. & McDermott, A. M. (2016). Microarray Analysis of Vitamin D Treated Human Corneal Epithelial Cells. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), MAY 01-05, 2016, Seattle, WA. Investigative Ophthalmology and Visual Science, 57(12)
Open this publication in new window or tab >>Microarray Analysis of Vitamin D Treated Human Corneal Epithelial Cells
2016 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed) Published
Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-204141 (URN)000394210205172 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), MAY 01-05, 2016, Seattle, WA
Note

QC 20170328

Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2017-11-29Bibliographically approved
Zhu, J., Zhao, C., Zhuang, T., Jonsson, P., Sinha, I., Williams, C., . . . Dahlman-Wright, K. (2016). RING finger protein 31 promotes p53 degradation in breast cancer cells. Oncogene, 35(15), 1955-1964
Open this publication in new window or tab >>RING finger protein 31 promotes p53 degradation in breast cancer cells
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2016 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 35, no 15, p. 1955-1964Article in journal (Refereed) Published
Abstract [en]

The atypical E3 ubiquitin ligase RNF31 is highly expressed in human breast cancer, the most frequent neoplastic lethality among women. Here, RNF31 depletion in breast cancer cells in combination with global gene expression profiling revealed p53 (TP53) signaling as a potential RNF31 target. Interestingly, RNF31 decreased p53 stability, whereas depletion of RNF31 in breast cancer cells caused cell cycle arrest and cisplatin-induced apoptosis in a p53-dependent manner. Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical data sets displayed a negative correlation between RNF31 and p53 target genes, including IGFBP3 and BTG1, consistent with RNF31 regulating p53 function in vivo as well. Together, our findings suggest RNF31 as a potential therapeutic target to restore p53 function in breast cancer.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
Keywords
ESTROGEN-RECEPTOR-ALPHA, MDM2 ANTAGONIST NUTLIN-3, UBIQUITIN LIGASE ACTIVITY, TRANSCRIPTIONAL REPRESSION, GERMLINE POLYMORPHISMS, ONCOPROTEIN MDM2, APOPTOSIS, E3, ACTIVATION, MUTATIONS
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-186617 (URN)10.1038/onc.2015.260 (DOI)000374010300008 ()26148235 (PubMedID)2-s2.0-84935442275 (Scopus ID)
Note

QC 20160531

Available from: 2016-05-31 Created: 2016-05-13 Last updated: 2018-01-10Bibliographically approved
Dey, P., Velazquez-Villegas, L. A., Faria, M., Turner, A., Jonsson, P., Webb, P., . . . Ström, A. M. (2015). Estrogen Receptor beta 2 Induces Hypoxia Signature of Gene Expression by Stabilizing HIF-1 alpha in Prostate Cancer. PLoS ONE, 10(5), Article ID e0128239.
Open this publication in new window or tab >>Estrogen Receptor beta 2 Induces Hypoxia Signature of Gene Expression by Stabilizing HIF-1 alpha in Prostate Cancer
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0128239Article in journal (Refereed) Published
Abstract [en]

The estrogen receptor (ER) beta variant ER beta 2 is expressed in aggressive castration-resistant prostate cancer and has been shown to correlate with decreased overall survival. Genome-wide expression analysis after ER beta 2 expression in prostate cancer cells revealed that hypoxia was an overrepresented theme. Here we show that ER beta 2 interacts with and stabilizes HIF-1 alpha protein in normoxia, thereby inducing a hypoxic gene expression signature. HIF-1 alpha is known to stimulate metastasis by increasing expression of Twist1 and increasing vascularization by directly activating VEGF expression. We found that ER beta 2 interacts with HIF-1 alpha and piggybacks to the HIF-1 alpha response element present on the proximal Twist1 and VEGF promoters. These findings suggest that at least part of the oncogenic effects of ER beta 2 is mediated by HIF-1 alpha and that targeting of this ER beta 2 -HIF-1 alpha interaction may be a strategy to treat prostate cancer.

Keywords
Tumor-Suppressor Protein, Hippel-Lindau Protein, Androgen Receptor, Er-Beta, Alpha, Growth, Hif, Transcription, Metastasis, Mechanism
National Category
Biological Sciences Medical and Health Sciences
Identifiers
urn:nbn:se:kth:diva-169966 (URN)10.1371/journal.pone.0128239 (DOI)000355183900212 ()26010887 (PubMedID)2-s2.0-84930221880 (Scopus ID)
Funder
Swedish Cancer SocietyEU, FP7, Seventh Framework Programme, GROWTH 291795Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20150625

Available from: 2015-06-25 Created: 2015-06-25 Last updated: 2017-12-04Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0602-2062

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