Alteration of oestradiol metabolism in myc oncogene-transfected mouse mammary epithelial cells.
Targeted overexpression of the c-myc oncogene induces neoplastic transformation in immortalized, non-tumorigenic mouse mammary epithelial cells (MMEC). Experiments in the present study were conducted to examine whether cellular transformation induced by c-myc oncogene is associated with altered metabolism of 17beta-oestradiol (E2). The parental, MMEC and the stable c-myc transfectant (MMEC/myc3) cell lines were compared for major oestrogen metabolic pathways, namely E2 and E1 interconversion, and C2- and C16alpha-hydroxylation by both high-pressure liquid chromatography (HPLC) analysis and the 3H release assay using specifically labelled [C2-3H]E2 or [C16alpha-3H]E2. The reductive conversion of E1 to E2 was about 14-fold and 12-fold higher than the oxidative conversion of E2 to E1 in MMEC and MMEC/myc3 cells respectively. However, in MMEC/myc3 cells, both reductive and oxidative reactions were decreased by about 32% and 12% relative to those seen in the parental MMEC cells (P = 0.0028). The extent of C16alpha-hydroxylation was increased by 164.3% (P < 0.001), with a concomitant 48.4% decrease (P < 0.001) in C2-hydroxylation in MMEC/myc3 cells; this resulted in a fourfold increase in the C16alpha/C2 hydroxylation ratio in this cell line. Thus, a persistent c-myc expression, leading to aberrant hyperproliferation in vitro and tumorigenesis in vivo, is associated with an altered oestrogen metabolism. However, it remains unclear whether this represents a result of oncogene expression/activation or is rather a consequence of phenotypic transformation of the cells.
Telang
N T
NT
Strang Cancer Research Laboratory, The Rockefeller University, New York, USA.
Arcuri
F
F
Granata
O M
OM
Bradlow
H L
HL
Osborne
M P
MP
Castagnetta
L
L
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism*; D016259:Genes, myc; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D014162:Transfection
D014408:Biomarkers, Tumor; D004958:Estradiol; D006913:Hydroxysteroid Dehydrogenases