PMID- 25530422
OWN - NLM
STAT- MEDLINE
DCOM- 20150805
LR  - 20211203
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 137
IP  - 3
DP  - 2015 Aug 1
TI  - The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen 
      receptor-positive breast cancer.
PG  - 686-97
LID - 10.1002/ijc.29404 [doi]
AB  - Around 70% of breast cancers express the estrogen receptor alpha (ERalpha) and depend on 
      estrogen for growth, survival and disease progression. The presence of hormone 
      sensitivity is usually associated with a favorable prognosis. Use of adjuvant 
      anti-endocrine therapy has significantly decreased breast cancer mortality in 
      patients with early-stage disease, and anti-endocrine therapy also plays a 
      central role in the treatment of advanced stages. However a subset of hormone 
      receptor-positive breast cancers do not benefit from anti-endocrine therapy, and 
      nearly all hormone receptor-positive metastatic breast cancers ultimately develop 
      resistance to anti-hormonal therapies. Despite new insights into mechanisms of 
      anti-endocrine therapy resistance, e.g., crosstalk between ERalpha and Her2/neu, the 
      management of advanced hormone-receptor-positive breast cancers that are 
      resistant to anti-endocrine agents remains a significant challenge. In the 
      present study, we demonstrate that the proteasome inhibitor Bortezomib strongly 
      inhibits ERalpha and HER2/neu expression, increases expression of cyclin-dependent 
      kinase inhibitors, inhibits expression of multiple genes associated with poor 
      prognosis in ERalpha+ breast cancer patients and induces cell death in ER+ breast 
      cancer cells in both the presence and absence of functional p53. Although 
      Bortezomib increased the levels of p53 and increased the expression of 
      pro-apoptotic target genes in ERalpha+ breast cancer cells harboring wild-type p53, 
      Bortezomib also exerts anti-tumoral effects on ERalpha+ breast cancer cells through 
      suppression of ERalpha expression and inhibition of PI3K/Akt/mammalian target of 
      rapamycin (mTOR) and ERK signaling independently of functional p53. These 
      findings suggest that Bortezomib might have the potential to improve the 
      management of anti-endocrine therapy resistant ERalpha+ breast cancers independently 
      of their p53 status.
CI  - (c) 2014 UICC.
FAU - Thaler, Sonja
AU  - Thaler S
AD  - Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty 
      Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Thiede, Gitta
AU  - Thiede G
AD  - Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty 
      Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Hengstler, Jan G
AU  - Hengstler JG
AD  - IfADo-Leibniz Research Centre for Working Environment and Human Factors (IfADo), 
      Technical University of Dortmund, Dortmund, Germany.
FAU - Schad, Arno
AU  - Schad A
AD  - Department of Pathology, Johannes Gutenberg University, Mainz, Germany.
FAU - Schmidt, Marcus
AU  - Schmidt M
AD  - Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, 
      Germany.
FAU - Sleeman, Jonathan P
AU  - Sleeman JP
AD  - Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty 
      Mannheim, University of Heidelberg, Mannheim, Germany.
AD  - KIT Campus Nord, Institute for Toxicology and Genetics, Karlsruhe, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150108
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Pyrazines)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Boronic Acids/pharmacology/*therapeutic use
MH  - Bortezomib
MH  - Breast Neoplasms/*drug therapy/*metabolism/mortality/pathology
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - ErbB Receptors/metabolism
MH  - Estrogen Receptor alpha/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neoplasm Metastasis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Prognosis
MH  - Proteasome Inhibitors/pharmacology/*therapeutic use
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyrazines/pharmacology/*therapeutic use
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Her2 inhibition
OT  - estrogen receptor alpha inhibition
OT  - proteasome inhibition
EDAT- 2014/12/23 06:00
MHDA- 2015/08/06 06:00
CRDT- 2014/12/23 06:00
PHST- 2014/04/13 00:00 [received]
PHST- 2014/12/03 00:00 [accepted]
PHST- 2014/12/23 06:00 [entrez]
PHST- 2014/12/23 06:00 [pubmed]
PHST- 2015/08/06 06:00 [medline]
AID - 10.1002/ijc.29404 [doi]
PST - ppublish
SO  - Int J Cancer. 2015 Aug 1;137(3):686-97. doi: 10.1002/ijc.29404. Epub 2015 Jan 8.