Product of aromatase activity in intact LNCaP and MCF-7 human cancer cells.
We investigated conversion rates of androgens to estrogens in cultured, hormone-responsive prostate (LNCaP) and breast (MCF-7) human cancer cells. For this purpose, we adopted an intact cell analysis, whereby cells were incubated for different incubation times in the presence of close-to-physiological (1 nM) or supraphysiological (1 microM) concentrations of labelled androgen precursors, i.e. testosterone (T) and androstenedione (delta4Ad). The aromatase activity, as measured by estrogen formation, was detected in LNCaP cells (0.5 pmol/ml), even though to a significantly lower extent than in MCF-7 cells (5.4 pmol/ml), using 1 microM T after 72 h incubation. Surprisingly, LNCaP cells displayed a much higher aromatase activity when T was used as a substrate with respect to delta4Ad. In either cell line, T transformation to delta4Ad was relatively low, attaining only 2.8% in LNCaP and 7.5% MCF-7 cells. However, T was mostly converted to conjugates (over 95%), glucuronides and some sulphates, in LNCaP cells, whereas it was only partly converted to sulphates (<10%) in MCF-7 cells. Aromatase activity seems to be inconsistent in LNCaP cells, being strongly affected by culture conditions, especially by fetal calf serum (FCS). Further studies should assess the regulation of aromatase expression by serum or growth factors in different human cancer cells, also using anti-aromatase and/or anti-estrogen compounds, in different culture conditions.
Castagnetta
L A
LA
Experimental Oncology and Molecular Endocrinology Units, Palermo Branch of the National Cancer Institute of Genoa, c/o M. Ascoli Cancer Hospital Center, Sicily, Italy. lucashbl@unipa.it
Granata
O M
OM
Bellavia
V
V
Amodio
R
R
Scaccianoce
E
E
Notarbartolo
M
M
Follari
M R
MR
Miceli
M D
MD
Carruba
G
G
D000728:Androgens / Q000378:metabolism; D001141:Aromatase / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D000728:Androgens; D004967:Estrogens; D001141:Aromatase