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Reporter gene assay demonstrates functional differences in estrogen receptor activity in purified breast cancer cells: A pilot study
International journal of cancer, 2003-12, Vol.107 (5), p.700-706
Singh, Anjana
Ali, Simak
Kothari, Manish S.
De Bella, Manuela Tamburo
Smith, Clive
Timms, Emma
Slade, Martin J.
Foxwell, Brian M.
Coombes, R. Charles
2003
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Singh, Anjana
Ali, Simak
Kothari, Manish S.
De Bella, Manuela Tamburo
Smith, Clive
Timms, Emma
Slade, Martin J.
Foxwell, Brian M.
Coombes, R. Charles
Titel
Reporter gene assay demonstrates functional differences in estrogen receptor activity in purified breast cancer cells: A pilot study
Ist Teil von
International journal of cancer, 2003-12, Vol.107 (5), p.700-706
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2003
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Tamoxifen has contributed to a dramatic reduction in breast cancer mortality and recent results indicate that aromatase inhibitors may further improve survival in some patients. Nevertheless, a substantial proportion of patients become resistant to treatment. To date, with the exception of estrogen receptor (ER) determination by ligand binding or immunohistochemical techniques, there has been no way of predicting which of several therapies is indicated in particular patients. We describe a novel assay using the adenoviral gene delivery system to assess ER function in breast cancer cells derived directly from patients. The purification and short‐term culture of these cells has been recently described by our laboratory. Adenovirus containing an estrogen‐regulated β‐galactosidase reporter gene (ERE‐lacZ) was constructed and used to test ER activity in breast cancer cells derived from 18 patients with primary and 16 patients with metastatic cancer, under varying treatment schedules. The adenoviral assay enabled ER activity to be readily determined in purified cells from primary breast cancers and secondary sites. Breast cancers cells could be categorized on the basis of ER activity in the absence of ligand, the presence of estrogen or anti‐estrogens. In primary breast cancers, our results correlated with ER determination by immunohistochemistry in 78% of cases. In patients who had become resistant to tamoxifen, however, we found some in whom reporter activity was stimulated by tamoxifen and others whose tumors were either still estrogen responsive or completely unresponsive, irrespective of the original ER content. Our findings indicate that this reporter assay could be useful in decisions regarding use of adjuvant endocrine therapies in breast cancer. © 2003 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0020-7136
eISSN: 1097-0215
DOI: 10.1002/ijc.11469
Titel-ID: cdi_proquest_miscellaneous_71308563
Format
–
Schlagworte
adenoviral systems
,
Adenoviridae
,
Adenoviridae - genetics
,
Antineoplastic agents
,
beta-Galactosidase - genetics
,
Biological and medical sciences
,
breast cancer
,
Breast Neoplasms - pathology
,
Carcinoma, Ductal - pathology
,
Carcinoma, Small Cell - pathology
,
Chemotherapy
,
estrogen receptor
,
Estrogen Receptor alpha
,
Female
,
Genes, Reporter
,
Genetic Vectors
,
Gynecology. Andrology. Obstetrics
,
Humans
,
Mammary gland diseases
,
Medical sciences
,
Neoplasm Invasiveness
,
Pharmacology. Drug treatments
,
Receptors, Estrogen - metabolism
,
Receptors, Progesterone - metabolism
,
Recombinant Fusion Proteins - metabolism
,
Reproducibility of Results
,
Tumor Cells, Cultured
,
Tumors
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