| HRSTKA, Roman, Rudolf NENUTIL, A. FOURTOUNA, M. MASLON, C. NAUGHTON, S. LANGDON, E. MURRAY, A. LARIONOV, Katarína PETRÁKOVÁ, P. MULLER, M. DIXON, T. HUPP a Bořivoj VOJTĚŠEK. The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers. Oncogene. Great Britain: Nature Publishing Group, 2010, roč. 29, č. 34, s. 4838-4847. ISSN 0950-9232. Dostupné z: https://dx.doi.org/10.1038/onc.2010.228. |
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@article{923415,
author = {Hrstka, Roman and Nenutil, Rudolf and Fourtouna, A. and Maslon, M. and Naughton, C. and Langdon, S. and Murray, E. and Larionov, A. and Petráková, Katarína and Muller, P. and Dixon, M. and Hupp, T. and Vojtěšek, Bořivoj},
article_location = {Great Britain},
article_number = {34},
doi = {http://dx.doi.org/10.1038/onc.2010.228},
keywords = {AGR2; tamoxifen; letrozole; estrogen receptor; breast cancer},
language = {eng},
issn = {0950-9232},
journal = {Oncogene},
title = {The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers},
volume = {29},
year = {2010}
}
TY - JOUR
ID - 923415
AU - Hrstka, Roman - Nenutil, Rudolf - Fourtouna, A. - Maslon, M. - Naughton, C. - Langdon, S. - Murray, E. - Larionov, A. - Petráková, Katarína - Muller, P. - Dixon, M. - Hupp, T. - Vojtěšek, Bořivoj
PY - 2010
TI - The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers
JF - Oncogene
VL - 29
IS - 34
SP - 4838-4847
EP - 4838-4847
PB - Nature Publishing Group
SN - 09509232
KW - AGR2
KW - tamoxifen
KW - letrozole
KW - estrogen receptor
KW - breast cancer
N2 - Transcriptomic screens in breast cancer cell lines have identified a protein named anterior gradient-2 (AGR2) as a potentially novel oncogene overexpressed in estrogen receptor (ER) positive tumours. As targeting the ER is responsible for major improvements in cure rates and prevention of breast cancers, we have evaluated the prooncogenic function of AGR2 in anti-hormone therapeutic responses. We show that AGR2 expression promotes cancer cell survival in clonogenic assays and increases cell proliferation and viability in a range of cancer cell lines. Chromatin immunoprecipitation and reporter assays indicate that AGR2 is transcriptionally activated by estrogen through ER alpha. However, we also found that AGR2 expression is elevated rather than inhibited in response to tamoxifen, thus identifying a novel mechanism to account for an agonistic effect of the drug on a specific pro-oncogenic pathway. Consistent with these data, clinical analysis indicates that AGR2 expression is related to treatment failure in ER alpha-positive breast cancers treated with tamoxifen. In contrast, AGR2 is one of the most highly suppressed genes in cancers of responding patients treated with the anti-hormonal drug letrozole. These data indicate that the AGR2 pathway represents a novel pro-oncogenic pathway for evaluation as anti-cancer drug developments, especially therapies that by-pass the agonist effects of tamoxifen.
ER -
HRSTKA, Roman, Rudolf NENUTIL, A. FOURTOUNA, M. MASLON, C. NAUGHTON, S. LANGDON, E. MURRAY, A. LARIONOV, Katarína PETRÁKOVÁ, P. MULLER, M. DIXON, T. HUPP a Bořivoj VOJTĚŠEK. The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers. \textit{Oncogene}. Great Britain: Nature Publishing Group, 2010, roč.~29, č.~34, s.~4838-4847. ISSN~0950-9232. Dostupné z: https://dx.doi.org/10.1038/onc.2010.228.
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