Metabolism of lipoidal derivatives of estradiol-17β in human mammary cancer tissue and cell lines

Adams, J.B.; Vrahimis, R.; Young, C.E.

doi:10.1016/0960-0760(91)90376-g

Cited by 6 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More work is obviously needed on the enzyme in mammary cancer cells. In agreement with the studies of Katz et al [61], the activity of the esterase towards E2-1713 oleate as substrate was unaffected by growing MCF-7 cells in the presence of E 2 [58].…”

Section: Lipoidal Estrogen Esterase (Enzyme 5supporting

confidence: 88%

“…However, addition of dibutyryl c-AMP to cell cultures which had been allowed to accumulate [3H]Ez-L failed tO influence the rate of breakdown of the latter when [3H]E 2 was withdrawn. Addition of calcitonin to cultures of MCF-7 cells, which has been observed to increase c-AMP levels, was also without effect in similar experiments [58]. Thus, no direct evidence that the esterase in human breast cancer cells was under polypeptide hormonal control via c-AMP could be obtained.…”

Section: Lipoidal Estrogen Esterase (Enzyme 5mentioning

confidence: 56%

“…By measuring the rate of saturation of ER and the rate of formation of E2-L after exposure of MCF-7 and ZR-75-1 cells to [3HIE2, it was shown that -37% and -62% saturation, respectively, of ER by E 2 occurred within 4min. In this time, very little synthesis of E2-L occurred [58]. Thus E2-L does not appear to function in a transport mechanism for delivery of E 2 to nuclear receptors, but rather may act to capture E z as an exclusively intracellutar metabolite capable of being regenerated to E 2.…”

Section: Fattyacyl Coa: Estradiol-1713 Acyi Transferase (Enzyme 4 Fimentioning

confidence: 82%

“…This difference appears to be due to higher levels of the esterase which cleaves these lipoidal derivatives (see next Section) found in ER negative cells [58]. The esterase hydrolysed unsaturated fatty acid esters of E 2 at a greater rate than saturated fatty acid esters of E 2 [58], thus leading to differing relative compositions of E2-L in ER positive and negative cell lines.…”

Section: Fattyacyl Coa: Estradiol-1713 Acyi Transferase (Enzyme 4 Fimentioning

confidence: 90%

“…Thus, no direct evidence that the esterase in human breast cancer cells was under polypeptide hormonal control via c-AMP could be obtained. Despite this, the enzyme in these cells was very sensitive to diisopropyl ftuorophosphate [58,61], and it is too early to dismiss the possibility of a hormone-induced activation via phosphorylation. More work is obviously needed on the enzyme in mammary cancer cells.…”

Section: Lipoidal Estrogen Esterase (Enzyme 5mentioning

confidence: 92%

See 4 more Smart Citations

Enzymatic regulation of estradiol-17β concentrations in human breast cancer cells

Adams¹

1991

Breast Cancer Res Tr

View full text Add to dashboard Cite

Estradiol-17 beta is known to be involved in both the etiology and maintenance of growth of breast cancer. However, blood levels of the hormone do not reflect those found within the cells due to a number of transformations catalysed by enzymes which may be under metabolite and/or hormonal regulation. Recognition of the importance of the hormone microenvironment within the cell focuses attention on these enzymes and provides the subject for this review. An interplay between the sex hormones, estrogen and progestin, can control estradiol-17 beta concentrations in breast cancer cells at the level of key transforming enzymes. In addition, some enzymes catalyse production of biologically inert derivatives which are rapidly eliminated from the cell. Other enzymes catalyse the formation of derivatives which are exclusively intracellular and can act as reserve forms of the hormone. Yet others lead to estradiol-17 beta metabolites which are cytotoxic. An improved understanding of the enzymes and the role of the related metabolites can provide the opportunity for the development of new therapeutic agents.

show abstract

Section: Lipoidal Estrogen Esterase (Enzyme 5supporting

confidence: 88%

Section: Lipoidal Estrogen Esterase (Enzyme 5mentioning

confidence: 56%

Section: Fattyacyl Coa: Estradiol-1713 Acyi Transferase (Enzyme 4 Fimentioning

confidence: 82%

Section: Fattyacyl Coa: Estradiol-1713 Acyi Transferase (Enzyme 4 Fimentioning

confidence: 90%

Section: Lipoidal Estrogen Esterase (Enzyme 5mentioning

confidence: 92%

See 3 more Smart Citations

Enzymatic regulation of estradiol-17β concentrations in human breast cancer cells

Adams¹

1991

Breast Cancer Res Tr

View full text Add to dashboard Cite

show abstract

Metabolism of 17β-Estradiol in ACI Rat Liver and Mammary Gland After Chronic Estradiol Treatment

Mesía-Vela

Sánchez²,

Reuhl³

et al.

Hormonal Carcinogenesis IV

View full text Add to dashboard Cite

Aromatase inhibitor development for treatment of breast cancer

Masamura

Adlercreutz

Harvey

et al. 1995

Breast Cancer Res Tr

View full text Add to dashboard Cite

Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17 beta-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue. To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hr urine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Metabolism of lipoidal derivatives of estradiol-17β in human mammary cancer tissue and cell lines

Cited by 6 publications

References 22 publications

Enzymatic regulation of estradiol-17β concentrations in human breast cancer cells

Enzymatic regulation of estradiol-17β concentrations in human breast cancer cells

Metabolism of 17β-Estradiol in ACI Rat Liver and Mammary Gland After Chronic Estradiol Treatment

Aromatase inhibitor development for treatment of breast cancer

Contact Info

Product

Resources

About