17β-Estradiol metabolites affect some regulators of the MCF-7 cell cycle

Lottering, Mona-Liza; Kock, Maryna de; Viljoen, Theorickus C.; Grobler, C.J.S.; Seegers, J.C.

doi:10.1016/s0304-3835(96)04489-8

Cited by 24 publications

(23 citation statements)

References 30 publications

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“…35,36 Treatment of MCF-7 cells with estrogen was shown to increase PCNA levels during the S phase. 31,37 High PCNA expression also predicts early relapse and shorter survival in breast cancer patients. 38 On the other hand, MCM proteins are recruited to the cell cycle pre-replication complex and are essential for initiation of DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

CAPER, a novel regulator of human breast cancer progression

et al. 2014

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Section: Discussionmentioning

confidence: 99%

CAPER, a novel regulator of human breast cancer progression

et al. 2014

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“…Increased 16 -hydroxylation in women is associated with increased breast cancer risk (Muti et al 2000). 16 -Hydroxylated metabolites stimulate breast cancer cell growth, whereas the 2-hydroxylated estrogens inhibit cell growth (Ball et al 1972, Seegers et al 1989, Lottering et al 1992, Zhu & Conney 1998. 2-OHE 1 and 2-OHE 2 are rapidly converted to the monomethyl ethers, 2-ME 1 and 2-ME 2 respectively by the enzyme catechol-O-methyltransferase (COMT) (Ball et al 1972, Jefcoate et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of 16α-hydroxyestrone and 2-methoxyestradiol on cyclin D1 involving the transcription factor ATF-2 in MCF-7 breast cancer cells

Lewis¹,

Pestell²,

Albanese³

et al. 2005

Journal of Molecular Endocrinology

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We studied the effects of 2-methoxyestradiol (2-ME 2 ) and 16 -hydroxyestrone (16 -OHE 1 ), two metabolites of estradiol (E 2 ), on DNA synthesis, cell cycle progression and cyclin D1 protein levels in estrogen receptor-positive MCF-7 cells. E 2 and 16 -OHE 1 stimulated DNA synthesis, and 2-ME 2 inhibited the stimulatory effects of these agents. E 2 and 16 -OHE 1 stimulated the progression of cells from G 1 to S phase and this effect was attenuated by 2-ME 2 . Western blot analysis showed that E 2 and 16 -OHE 1 increased cyclin D1 protein level by about fourfold compared with control. 2-ME 2 had no significant effect on cyclin D1; however, it prevented the accumulation of cyclin D1 in the presence of E 2 and 16 -OHE 1 . Cells transfected with a cyclin D1 reporter gene and treated with E 2 or 16 -OHE 1 showed 7-and 9·5-fold increase respectively in promoter activity compared with control. This activity was significantly inhibited by 2-ME 2 . Cyclin D1 transactivation was mediated by the cAMP response element (CRE) region, which binds activating transcription factor 2 (ATF-2). DNA affinity assay showed 2·5-and 3·5-fold increases in ATF-2 binding to CRE in the presence of E 2 and 16 -OHE 1 respectively. The binding of ATF-2 was inhibited by the presence of 2-ME 2 . These results show that 2-ME 2 can downregulate cyclin D1 and thereby cell cycle progression by a mechanism involving the disruption of ATF-2 binding to cyclin D1 promoter.

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“…In pursuit to unravel possible mechanism of action of 2-ME, several molecular targets including reactive oxygen species (Lin et al, 2000), cell cycle kinases and regulators (Lottering et al, 1996;Zoubine et al, 1999), transcription factor modulators (Yue et al, 1997), p53, tubulin etc. (Mukhopadhyay and Roth, 1997;D'Amato et al, 1994;Hamel et al, 1996) have been proposed.…”

Section: Introductionmentioning

confidence: 99%

“…(Mukhopadhyay and Roth, 1997;D'Amato et al, 1994;Hamel et al, 1996) have been proposed. In breast cancer cells, the treatment of 2-ME caused cell cycle dependent alteration in the level of cyclic-AMP accompanied by changes in the phosphorylation pattern of various proteins (Lottering et al, 1996). 2-ME is also known to up regulate DR5 (death receptor) and sensitizes cells to TRAIL induced apoptosis (Ibrahim et al, 2001).…”

Section: Introductionmentioning

confidence: 99%