Biological effects of stable overexpression of aromatase in human hormone-dependent breast cancer cells

Aromatase is a key enzyme in the conversion of androstenedione and testosterone to oestrone and oestradiol. Intratumoral aromatase activity is expressed by around 70% of breast carcinomas, but it is not clear what effect this has on the tumour phenotype. To address this question we expressed human a...

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Bibliographic Details
Published in:British journal of cancer 1994-01, Vol.69 (1), p.77-83
Main Authors: Macaulay, VM, Nicholls, JE, Gledhill, J, Rowlands, MG, Dowsett, M, Ashworth, A
Format: Article
Language:English
Subjects:
Animals
Aromatase - genetics
Aromatase - metabolism
Aromatase - physiology
Base Sequence
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Breast Neoplasms - enzymology
Breast Neoplasms - genetics
Cancer Research
CHO Cells
Cricetinae
DNA, Complementary - genetics
Drug Resistance
Enzyme Stability
Epidemiology
experimental-oncology
Gene Expression - genetics
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Molecular Medicine
Molecular Sequence Data
Neoplasms, Hormone-Dependent - enzymology
Neoplasms, Hormone-Dependent - genetics
Oncology
Phenotype
Receptors, Estrogen - physiology
RNA, Messenger - genetics
Transfection
Tumor Cells, Cultured
Tumors
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Summary:Aromatase is a key enzyme in the conversion of androstenedione and testosterone to oestrone and oestradiol. Intratumoral aromatase activity is expressed by around 70% of breast carcinomas, but it is not clear what effect this has on the tumour phenotype. To address this question we expressed human aromatase in hormone-dependent MCF-7 breast cancer cells. Clone Arom. 1 expressed aromatase at 1,000 times the endogenous level in wild-type (WT) cells. Clone Arom. 2 incorporated the expression construct but did not express aromatase at levels above WT. There was no morphological difference between the two clones and WT, all three cell lines expressed oestrogen receptor at equivalent levels, and all manifested a mitogenic response to oestradiol. In steroid-depleted medium Arom. 1 cells showed significant growth enhancement over WT and Arom. 2, and this growth advantage was increased by exogenous androstenedione or testosterone. Both the enzyme activity and androgen-stimulated growth of Arom. 1 cells were completely reversible by aromatase inhibitor CGS 16949A. The Arom. 1 cell line may contribute to the development of an in vivo model of intratumoral aromatase, to study the biological significance of this phenomenon.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1994.12