Selective turnover of the essential fatty acid ester components of estradiol-17β lipoidal derivatives formed by human mammary cancer cells in culture

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Abstract

The properties of fatty acyl coenzyme A: estradiol-17β acyl transferase in microsomes derived from pooled human mammary cancer tissue have been examined. A pH optimum of 5.5 was found and addition of long-chained fatty acyl CoAs increased estradiol-17β (E2) 17-monoacyl ester synthesis; the apparent Km for E2 being 8μM when oleoyl CoA, linolenoyl CoA or palmitoyl CoA were employed. Testosterone, dehydroepiandrosterone, and 5-androstene-3β,17β-diol acted as competitive inhibitors with K1 values of 36, 36 and 46 μM, respectively. The composition of E2fatty acyl esters (E2-L) formed by incubation of [3h]e2 with human mammary cancer tissue and human mammary cancer cell lines has been determined by HPLC. Although the composition of E2-L in estrogen receptor negative cell lines (MDA-MB-231 and MDA-MB-330) was generally similar to that found for MCF-7 cells (estrogen receptor positive) and pooled human mammary cancer tissue, the former cell lines contained a 3-fold higher relative concentration of E2-17β stearate. MCF-7 cells were exposed to 30 nM [3h]e2and the composition of the isolated [3H]E2-L fraction studied at various time intervals. At 0.5 h, the intracellular concentration of E2-L was 1.8 ± 0.4 (SEM) pmol/mg DNA which increased to values of 3.6 ± 0.6 and 4.3 ± 0.5 at 4 h and 16 h, respectively. In the subsequent 3 h following transfer to medium lacking [3H]E2, the concentration of E2-L declined to 3.7 ± 0.3 pmol/mg DNA. The subfraction of E2-L composed of E2-17β arachidonate, linolenate and docosahexaenoate, was seen to decline in relative abundance after 0.5 h and to reach significantly lower relative levels at 16 h, and again in the 3 h period following estrogen withdrawal. The data suggests that these components, derived from essential fatty acids, are more metabolically active. This may then provide a new lead to link these novel estrogen derivatives with the established relationship between unsaturated fatty acids and an increased mammary cancer incidence.

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