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RHAMM splice variants confer radiosensitivity in human breast cancer cell lines

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RHAMM splice variants confer radiosensitivity in human breast cancer cell lines. / Schütze, Alexandra; Vogeley, Christian; Gorges, Tobias; Twarock, Sören; Butschan, Jonas; Babayan, Anna; Klein, Diana; Knauer, Shirley K; Metzen, Eric; Müller, Volkmar; Jendrossek, Verena; Pantel, Klaus; Milde-Langosch, Karin; Fischer, Jens W; Röck, Katharina.

in: ONCOTARGET, Jahrgang 7, Nr. 16, 08.02.2016, S. 21428-40.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schütze, A, Vogeley, C, Gorges, T, Twarock, S, Butschan, J, Babayan, A, Klein, D, Knauer, SK, Metzen, E, Müller, V, Jendrossek, V, Pantel, K, Milde-Langosch, K, Fischer, JW & Röck, K 2016, 'RHAMM splice variants confer radiosensitivity in human breast cancer cell lines', ONCOTARGET, Jg. 7, Nr. 16, S. 21428-40. https://doi.org/10.18632/oncotarget.7258

APA

Schütze, A., Vogeley, C., Gorges, T., Twarock, S., Butschan, J., Babayan, A., Klein, D., Knauer, S. K., Metzen, E., Müller, V., Jendrossek, V., Pantel, K., Milde-Langosch, K., Fischer, J. W., & Röck, K. (2016). RHAMM splice variants confer radiosensitivity in human breast cancer cell lines. ONCOTARGET, 7(16), 21428-40. https://doi.org/10.18632/oncotarget.7258

Vancouver

Schütze A, Vogeley C, Gorges T, Twarock S, Butschan J, Babayan A et al. RHAMM splice variants confer radiosensitivity in human breast cancer cell lines. ONCOTARGET. 2016 Feb 8;7(16):21428-40. https://doi.org/10.18632/oncotarget.7258

Bibtex

@article{8052b89a3f9441bcb512b4f2b3c12b60,
title = "RHAMM splice variants confer radiosensitivity in human breast cancer cell lines",
abstract = "Biomarkers for prognosis in radiotherapy-treated breast cancer patients are urgently needed and important to stratify patients for adjuvant therapies. Recently, a role of the receptor of hyaluronan-mediated motility (RHAMM) has been suggested for tumor progression. Our aim was (i) to investigate the prognostic value of RHAMM in breast cancer and (ii) to unravel its potential function in the radiosusceptibility of breast cancer cells. We demonstrate that RHAMM mRNA expression in breast cancer biopsies is inversely correlated with tumor grade and overall survival. Radiosusceptibility in vitro was evaluated by sub-G1 analysis (apoptosis) and determination of the proliferation rate. The potential role of RHAMM was addressed by short interfering RNAs against RHAMM and its splice variants. High expression of RHAMMv1/v2 in p53 wild type cells (MCF-7) induced cellular apoptosis in response to ionizing radiation. In comparison, in p53 mutated cells (MDA-MB-231) RHAMMv1/v2 was expressed sparsely resulting in resistance towards irradiation induced apoptosis. Proliferation capacity was not altered by ionizing radiation in both cell lines. Importantly, pharmacological inhibition of the major ligand of RHAMM, hyaluronan, sensitized both cell lines towards radiation induced cell death. Based on the present data, we conclude that the detection of RHAMM splice variants in correlation with the p53 mutation status could help to predict the susceptibility of breast cancer cells to radiotherapy. Additionally, our studies raise the possibility that the response to radiotherapy in selected cohorts may be improved by pharmaceutical strategies against RHAMM and its ligand hyaluronan.",
author = "Alexandra Sch{\"u}tze and Christian Vogeley and Tobias Gorges and S{\"o}ren Twarock and Jonas Butschan and Anna Babayan and Diana Klein and Knauer, {Shirley K} and Eric Metzen and Volkmar M{\"u}ller and Verena Jendrossek and Klaus Pantel and Karin Milde-Langosch and Fischer, {Jens W} and Katharina R{\"o}ck",
year = "2016",
month = feb,
day = "8",
doi = "10.18632/oncotarget.7258",
language = "English",
volume = "7",
pages = "21428--40",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "16",

}

RIS

TY - JOUR

T1 - RHAMM splice variants confer radiosensitivity in human breast cancer cell lines

AU - Schütze, Alexandra

AU - Vogeley, Christian

AU - Gorges, Tobias

AU - Twarock, Sören

AU - Butschan, Jonas

AU - Babayan, Anna

AU - Klein, Diana

AU - Knauer, Shirley K

AU - Metzen, Eric

AU - Müller, Volkmar

AU - Jendrossek, Verena

AU - Pantel, Klaus

AU - Milde-Langosch, Karin

AU - Fischer, Jens W

AU - Röck, Katharina

PY - 2016/2/8

Y1 - 2016/2/8

N2 - Biomarkers for prognosis in radiotherapy-treated breast cancer patients are urgently needed and important to stratify patients for adjuvant therapies. Recently, a role of the receptor of hyaluronan-mediated motility (RHAMM) has been suggested for tumor progression. Our aim was (i) to investigate the prognostic value of RHAMM in breast cancer and (ii) to unravel its potential function in the radiosusceptibility of breast cancer cells. We demonstrate that RHAMM mRNA expression in breast cancer biopsies is inversely correlated with tumor grade and overall survival. Radiosusceptibility in vitro was evaluated by sub-G1 analysis (apoptosis) and determination of the proliferation rate. The potential role of RHAMM was addressed by short interfering RNAs against RHAMM and its splice variants. High expression of RHAMMv1/v2 in p53 wild type cells (MCF-7) induced cellular apoptosis in response to ionizing radiation. In comparison, in p53 mutated cells (MDA-MB-231) RHAMMv1/v2 was expressed sparsely resulting in resistance towards irradiation induced apoptosis. Proliferation capacity was not altered by ionizing radiation in both cell lines. Importantly, pharmacological inhibition of the major ligand of RHAMM, hyaluronan, sensitized both cell lines towards radiation induced cell death. Based on the present data, we conclude that the detection of RHAMM splice variants in correlation with the p53 mutation status could help to predict the susceptibility of breast cancer cells to radiotherapy. Additionally, our studies raise the possibility that the response to radiotherapy in selected cohorts may be improved by pharmaceutical strategies against RHAMM and its ligand hyaluronan.

AB - Biomarkers for prognosis in radiotherapy-treated breast cancer patients are urgently needed and important to stratify patients for adjuvant therapies. Recently, a role of the receptor of hyaluronan-mediated motility (RHAMM) has been suggested for tumor progression. Our aim was (i) to investigate the prognostic value of RHAMM in breast cancer and (ii) to unravel its potential function in the radiosusceptibility of breast cancer cells. We demonstrate that RHAMM mRNA expression in breast cancer biopsies is inversely correlated with tumor grade and overall survival. Radiosusceptibility in vitro was evaluated by sub-G1 analysis (apoptosis) and determination of the proliferation rate. The potential role of RHAMM was addressed by short interfering RNAs against RHAMM and its splice variants. High expression of RHAMMv1/v2 in p53 wild type cells (MCF-7) induced cellular apoptosis in response to ionizing radiation. In comparison, in p53 mutated cells (MDA-MB-231) RHAMMv1/v2 was expressed sparsely resulting in resistance towards irradiation induced apoptosis. Proliferation capacity was not altered by ionizing radiation in both cell lines. Importantly, pharmacological inhibition of the major ligand of RHAMM, hyaluronan, sensitized both cell lines towards radiation induced cell death. Based on the present data, we conclude that the detection of RHAMM splice variants in correlation with the p53 mutation status could help to predict the susceptibility of breast cancer cells to radiotherapy. Additionally, our studies raise the possibility that the response to radiotherapy in selected cohorts may be improved by pharmaceutical strategies against RHAMM and its ligand hyaluronan.

U2 - 10.18632/oncotarget.7258

DO - 10.18632/oncotarget.7258

M3 - SCORING: Journal article

C2 - 26870892

VL - 7

SP - 21428

EP - 21440

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 16

ER -