TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

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Standard

TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line. / Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel; Jensen, Vibeke; Stenvang, Jan; Yang, Huanming; Brünner, Nils; Rasmussen, Anne-Sofie Schrohl.

In: Tumor Biology, Vol. 34, No. 2, 2013, p. 1161-1170.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Deng, X, Fogh, L, Lademann, UA, Jensen, V, Stenvang, J, Yang, H, Brünner, N & Rasmussen, A-SS 2013, 'TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line', Tumor Biology, vol. 34, no. 2, pp. 1161-1170. https://doi.org/10.1007/s13277-013-0659-5

APA

Deng, X., Fogh, L., Lademann, U. A., Jensen, V., Stenvang, J., Yang, H., Brünner, N., & Rasmussen, A-S. S. (2013). TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line. Tumor Biology, 34(2), 1161-1170. https://doi.org/10.1007/s13277-013-0659-5

Vancouver

Deng X, Fogh L, Lademann UA, Jensen V, Stenvang J, Yang H et al. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line. Tumor Biology. 2013;34(2):1161-1170. https://doi.org/10.1007/s13277-013-0659-5

Author

Deng, Xiaohong ; Fogh, Louise ; Lademann, Ulrik Axel ; Jensen, Vibeke ; Stenvang, Jan ; Yang, Huanming ; Brünner, Nils ; Rasmussen, Anne-Sofie Schrohl. / TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line. In: Tumor Biology. 2013 ; Vol. 34, No. 2. pp. 1161-1170.

Bibtex

@article{884c8e49e13c489783c9459233378f84,
title = "TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line",
abstract = "Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested as a marker of prognosis and response to treatment in breast cancer. In vitro, TIMP-1 can regulate shedding of the extracellular domain of HER2 and signalling via the Akt pathway, and we hypothesize that TIMP-1 therefore can affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of TIMP-1 protein. Western blotting showed that the activation of Akt, PTEN, and HER2 as well as ADAM10 was similar in all clones. In conclusion, in this model, TIMP-1 overexpression does not affect HER2 cleavage by ADAM10 or signalling via the Akt pathway, and TIMP-1 does not influence sensitivity to trastuzumab and lapatinib.",
keywords = "Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Apoptosis, Blotting, Western, Breast Neoplasms, Cell Proliferation, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, PTEN Phosphohydrolase, Phosphorylation, Proto-Oncogene Proteins c-akt, Quinazolines, Receptor, erbB-2, Tissue Inhibitor of Metalloproteinase-1, Tumor Cells, Cultured",
author = "Xiaohong Deng and Louise Fogh and Lademann, {Ulrik Axel} and Vibeke Jensen and Jan Stenvang and Huanming Yang and Nils Br{\"u}nner and Rasmussen, {Anne-Sofie Schrohl}",
year = "2013",
doi = "10.1007/s13277-013-0659-5",
language = "English",
volume = "34",
pages = "1161--1170",
journal = "Tumor Biology",
issn = "1010-4283",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

AU - Deng, Xiaohong

AU - Fogh, Louise

AU - Lademann, Ulrik Axel

AU - Jensen, Vibeke

AU - Stenvang, Jan

AU - Yang, Huanming

AU - Brünner, Nils

AU - Rasmussen, Anne-Sofie Schrohl

PY - 2013

Y1 - 2013

N2 - Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested as a marker of prognosis and response to treatment in breast cancer. In vitro, TIMP-1 can regulate shedding of the extracellular domain of HER2 and signalling via the Akt pathway, and we hypothesize that TIMP-1 therefore can affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of TIMP-1 protein. Western blotting showed that the activation of Akt, PTEN, and HER2 as well as ADAM10 was similar in all clones. In conclusion, in this model, TIMP-1 overexpression does not affect HER2 cleavage by ADAM10 or signalling via the Akt pathway, and TIMP-1 does not influence sensitivity to trastuzumab and lapatinib.

AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested as a marker of prognosis and response to treatment in breast cancer. In vitro, TIMP-1 can regulate shedding of the extracellular domain of HER2 and signalling via the Akt pathway, and we hypothesize that TIMP-1 therefore can affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of TIMP-1 protein. Western blotting showed that the activation of Akt, PTEN, and HER2 as well as ADAM10 was similar in all clones. In conclusion, in this model, TIMP-1 overexpression does not affect HER2 cleavage by ADAM10 or signalling via the Akt pathway, and TIMP-1 does not influence sensitivity to trastuzumab and lapatinib.

KW - Antibodies, Monoclonal, Humanized

KW - Antineoplastic Agents

KW - Apoptosis

KW - Blotting, Western

KW - Breast Neoplasms

KW - Cell Proliferation

KW - Drug Resistance, Neoplasm

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - PTEN Phosphohydrolase

KW - Phosphorylation

KW - Proto-Oncogene Proteins c-akt

KW - Quinazolines

KW - Receptor, erbB-2

KW - Tissue Inhibitor of Metalloproteinase-1

KW - Tumor Cells, Cultured

U2 - 10.1007/s13277-013-0659-5

DO - 10.1007/s13277-013-0659-5

M3 - Journal article

C2 - 23334956

VL - 34

SP - 1161

EP - 1170

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 2

ER -

ID: 59301571