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 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.
Macaulay
V M
VM
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Nicholls
J E
JE
Gledhill
J
J
Rowlands
M G
MG
Dowsett
M
M
Ashworth
A
A
D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D016466:CHO Cells; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D004795:Enzyme Stability; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology* / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D001141:Aromatase