This study examined the enzymatic characteristics and steroid regulation of the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) in the human breast cancer cell line T-47D. In cell homogenates, exogenous NAD significantly increased the conversion of corticosterone to 11-dehydrocorticosterone, while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11β-HSD2 in T-47D cells, while 11β-HSD1 mRNA levels were undetectable. In T-47D cells treated for 24 h with medroxyprogesterone acetate (MPA), 11β-HSD catalytic activity was elevated 11-fold, while estrone (E1), estradiol (E2) and the synthetic glucocorticoid dexamethasone (DEX) were ineffective. The antiprogestin mifepristone (RU486) acted as a pure antagonist of the progestin-enhanced 11β-HSD activity, but did not exert any agonistic effects of its own. In addition, RT-PCR analysis demonstrated that MPA was a potent inducer of 11β-HSD2 gene expression, increasing the steady-state levels of 11β-HSD2 mRNA. Taken together, these results demonstrate that 11β-HSD2 is the 11β-HSD isoform expressed by T-47D cells under steady-state conditions and suggest the existence of a previously undocumented mechanism of action of progestins in breast cancer cells.

Arcuri, F., Sestini, S., Ricci, C., Runci, Y., Carducci, A., Ricci, L., et al. (2000). Progestin regulation of 11beta-hydroxysteroid dehydrogenase expression in T-47D human breast cancer cells. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 72(5), 239-247 [10.1016/S0960-0760(00)00039-X].

Progestin regulation of 11beta-hydroxysteroid dehydrogenase expression in T-47D human breast cancer cells

ARCURI, F.;SESTINI, S.;RICCI, C.;RICCI, L.;CINTORINO, M.
2000-01-01

Abstract

This study examined the enzymatic characteristics and steroid regulation of the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) in the human breast cancer cell line T-47D. In cell homogenates, exogenous NAD significantly increased the conversion of corticosterone to 11-dehydrocorticosterone, while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11β-HSD2 in T-47D cells, while 11β-HSD1 mRNA levels were undetectable. In T-47D cells treated for 24 h with medroxyprogesterone acetate (MPA), 11β-HSD catalytic activity was elevated 11-fold, while estrone (E1), estradiol (E2) and the synthetic glucocorticoid dexamethasone (DEX) were ineffective. The antiprogestin mifepristone (RU486) acted as a pure antagonist of the progestin-enhanced 11β-HSD activity, but did not exert any agonistic effects of its own. In addition, RT-PCR analysis demonstrated that MPA was a potent inducer of 11β-HSD2 gene expression, increasing the steady-state levels of 11β-HSD2 mRNA. Taken together, these results demonstrate that 11β-HSD2 is the 11β-HSD isoform expressed by T-47D cells under steady-state conditions and suggest the existence of a previously undocumented mechanism of action of progestins in breast cancer cells.
2000
Arcuri, F., Sestini, S., Ricci, C., Runci, Y., Carducci, A., Ricci, L., et al. (2000). Progestin regulation of 11beta-hydroxysteroid dehydrogenase expression in T-47D human breast cancer cells. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 72(5), 239-247 [10.1016/S0960-0760(00)00039-X].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/27734
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