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  • Magnusson, Kristina,1979-Uppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén (author)

ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-11-18
  • BioMed Central,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-197768
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-197768URI
  • https://doi.org/10.1186/s12885-016-2923-8DOI
  • https://lup.lub.lu.se/record/da699b64-2598-488a-b644-1ec4686051d4URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-264237URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20161229
  • Background: Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Methods: Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. Results: High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1. Conclusions: ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.

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  • Gremel, GabrielaUppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén(Swepub:uu)gabgr787 (author)
  • Rydén, LisaLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Clinical Sciences, Division of Surgery, Lund University.(Swepub:lu)pat-lry (author)
  • Ponten, VictorUppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)
  • Uhlén, MathiasKTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Science for Life Laboratory, KTH – Royal Institute of Technology, Stockholm(Swepub:kth)u1dulvmw (author)
  • Dimberg, AnnaUppsala universitet,Uppsala University,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Anna Dimberg(Swepub:uu)annadimb (author)
  • Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund.(Swepub:lu)pat-kji (author)
  • Pontén, FredrikUppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén(Swepub:uu)fredpont (author)
  • Uppsala UniversityInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

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  • In:BMC Cancer: BioMed Central161471-2407

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By the author/editor
Magnusson, Krist ...
Gremel, Gabriela
Rydén, Lisa
Ponten, Victor
Uhlén, Mathias
Dimberg, Anna
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Jirström, Karin
Pontén, Fredrik
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
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BMC Cancer
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Royal Institute of Technology
Lund University
Uppsala University

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Kristina_Magnusson
Magnusson, Kristina,1979-
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