Control of aromatase in breast cancer cells and its importance for tumor growth.
Three approaches have been taken to elucidate further the biological importance of intratumoural aromatase activity. (i) MCF7 and T47D hormone-dependent breast cancer cell lines both showed detectable aromatase activity in vitro. The up-regulation of this by TGF alpha indicates the possible existence of an autocrine growth stimulatory loop involving aromatase. (ii) Both tamoxifen and cytotoxic chemotherapy caused the suppression of aromatase activity in breast carcinomas in vivo. Aromatase activity prior to treatment did not predict for clinical response to tamoxifen. (iii) Transfection of aromatase into MCF7 cells led to their growth being stimulated by low doses of androgens and this was inhibited by the aromatase inhibitor CGS 16949A.
Academic Department of Biochemistry, Royal Marsden Hospital, London, England.
M
M
Dowsett
V
V
Macaulay
J
J
Gledhill
C
C
Ryde
J
J
Nicholls
A
A
Ashworth
J A
JA
McKinna
I E
IE
Smith
D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology; D005260:Female; D006801:Humans; D013739:Testosterone / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016211:Transforming Growth Factor alpha; D013739:Testosterone; D004815:Epidermal Growth Factor; D003994:Bucladesine; D001141:Aromatase; D017316:Fadrozole