Abstract | BACKGROUND: MATERIALS AND METHODS: To investigate the mechanisms involved in the loss of sensitivity of the tumors to AIs, we developed a cell line isolated from the tumors of long-term letrozole-treated MCF-7Ca xenografts. This cell line was designated LTLT-Ca. RESULTS: CONCLUSION: Our data suggest that inhibition of both the HER2 and estrogen signaling pathways is required to prolong the responsiveness of the tumors to endocrine therapies. In addition, we have shown that HER2 upregulation is an adaptive process that the tumors undergo during continued letrozole treatment, which is reversed upon removal of the treatment. The tumors regain responsiveness to letrozole after a short period "off" treatment. These studies suggest that by reversing the resistance to hormone therapy, patients could have a second response and could delay the need for chemotherapy.
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Authors | Gauri Sabnis, Angela Brodie |
Journal | Clinical breast cancer
(Clin Breast Cancer)
Vol. 10
Issue 1
Pg. E6-E15
(Feb 2010)
ISSN: 1938-0666 [Electronic] United States |
PMID | 20133251
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents, Hormonal
- Estrogen Receptor alpha
- Nitriles
- Triazoles
- Letrozole
- Aromatase
- Receptor, ErbB-2
- Trastuzumab
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Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents, Hormonal
(pharmacology)
- Aromatase
(genetics)
- Breast Neoplasms
(genetics, metabolism)
- Cell Line, Tumor
- Disease Models, Animal
- Drug Resistance, Neoplasm
(genetics)
- Estrogen Receptor alpha
(genetics)
- Female
- Humans
- Letrozole
- Mice
- Mice, Nude
- Neoplasms, Hormone-Dependent
(genetics, metabolism)
- Nitriles
(pharmacology)
- Ovariectomy
- Receptor, ErbB-2
(metabolism)
- Signal Transduction
(drug effects, physiology)
- Transfection
- Trastuzumab
- Triazoles
(pharmacology)
- Xenograft Model Antitumor Assays
(methods)
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