Abstract | BACKGROUND: METHODS: Using extracts of fresh invasive ERalpha-positive invasive breast carcinomas, ductal carcinoma in situ, and normal glandular breast tissue, the authors performed Western blot analyses of the membrane-bound ER, 1 of its phosphorylated isoforms, and cytosolic fractions from the same specimens, examining associated proteins (Akt/ mitogen-activated protein kinase pathways). Western blot analysis and immunocapture for the apoptosis and survival factors Bcl-2 agonist of death (BAD)/Bcl-2 and BAD/Bcl-xL were also performed. RESULTS: To the authors' knowledge, this is the first study to report that ERalpha was phosphorylated in the plasma membrane fractions derived from patients' invasive breast carcinomas. This was associated with a predominance of phosphorylated BAD and a relative reduction in Bcl-2 compared with both normal tissue and ductal carcinoma in situ, although such studies in fresh tissue did not corroborate these findings. The authors also demonstrated that the BAD/Bcl-2 and BAD/Bcl-xL complexes characterized the invasive carcinoma state. CONCLUSIONS: A phosphorylated form of the membrane ER was found to characterize the invasive cancer state. This was associated with a reduction in BAD/Bcl-2 and BAD/Bcl-xl. These data implicate the membrane ERalpha as the in vivo receptor responsible for transcription-independent cellular responses to estrogens.
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Authors | Paul J Mintz, Nagy A Habib, Louise J Jones, Georgios Giamas, Jacqueline S Lewis, Rebecca L Bowen, R Charles Coombes, Justin Stebbing |
Journal | Cancer
(Cancer)
Vol. 113
Issue 6
Pg. 1489-95
(Sep 15 2008)
ISSN: 0008-543X [Print] United States |
PMID | 18615623
(Publication Type: Journal Article)
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Copyright | (c) 2008 American Cancer Society. |
Chemical References |
- BAD protein, human
- BCL2L1 protein, human
- ESR1 protein, human
- Estrogen Receptor alpha
- Estrogens
- Proto-Oncogene Proteins c-bcl-2
- bcl-Associated Death Protein
- bcl-X Protein
- Proto-Oncogene Proteins c-akt
- Mitogen-Activated Protein Kinases
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Topics |
- Aged
- Aged, 80 and over
- Apoptosis
(physiology)
- Breast
(metabolism, pathology)
- Breast Neoplasms
(metabolism, pathology)
- Carcinoma, Ductal, Breast
(metabolism, pathology)
- Carcinoma, Intraductal, Noninfiltrating
(metabolism, pathology)
- Cell Membrane
(metabolism, pathology)
- Cytoplasm
(metabolism, pathology)
- Cytosol
(metabolism, pathology)
- Estrogen Receptor alpha
(metabolism)
- Estrogens
(pharmacology)
- Female
- Humans
- Immunoprecipitation
- Middle Aged
- Mitogen-Activated Protein Kinases
(metabolism)
- Neoplasm Invasiveness
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Signal Transduction
- Tumor Cells, Cultured
- bcl-Associated Death Protein
(metabolism)
- bcl-X Protein
(metabolism)
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