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

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

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

Gremel, Gabriela (författare): Uppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén

Rydén, Lisa (författare): Lund 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.

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Ponten, Victor (författare): Uppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab

Uhlén, Mathias (författare): KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Science for Life Laboratory, KTH – Royal Institute of Technology, Stockholm

Dimberg, Anna (författare): Uppsala universitet,Uppsala University,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Anna Dimberg

Jirström, Karin (författare): Lund 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.

Pontén, Fredrik (författare): Uppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén

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2016-11-18
2016
Engelska.
Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 16

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Abstract Ämnesord

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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

ANLN
Prognostic biomarker
Breast cancer
Proliferation
Antibody-based proteomics
ANLN
Antibody-based proteomics
Breast cancer
Prognostic biomarker
Proliferation

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Av författaren/redakt...: Magnusson, Krist ...; Gremel, Gabriela; Rydén, Lisa; Ponten, Victor; Uhlén, Mathias; Dimberg, Anna; visa fler...; Jirström, Karin; Pontén, Fredrik; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Artiklar i publikationen: BMC Cancer

Av lärosätet: Kungliga Tekniska Högskolan; Lunds universitet; Uppsala universitet

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