Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo

Sömjen, Dalia; Waisman, A.; Kaye, Alvin M.

doi:10.1016/s0960-0760(96)00135-5

Cited by 49 publications

(26 citation statements)

References 32 publications

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“…Second, under various experimental conditions the combined effects of estradiol and antiestrogens were consistent with competitive inhibition. For example, both estradiol and TAM (or RAL) increased DNA synthesis, but in accordance with observations in other estrogen responsive tissues, 18 this effect was not . In other incubates, cells were exposed to both E 2 (30 nmol/L) and either E15 (2.5 g/mL) or (FabЈ) (2.5 g/mL).…”

Section: Discussionsupporting

confidence: 81%

Effects of Gonadal Steroids and Their Antagonists on DNA Synthesis in Human Vascular Cells

et al. 1998

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Abstract-The cardiovascular effect of estrogen is currently under intense investigation, but the role of androgens in vascular biology has attracted little attention. Because endothelial repair and vascular smooth muscle cell (VSMC) proliferation affect atherogenesis, we analyzed the effects of 17␤-estradiol (E 2 ), dihydrotestosterone (DHT), and sex hormone antagonists on DNA synthesis in human umbilical VSMCs and in E304 cells (a human umbilical endothelial cell line). In VSMCs, both E 2 and DHT had a biphasic effect on [ 3 H]thymidine incorporation into DNA: low concentrations (0.3 nmol/L for E 2 , 3 nmol/L for DHT) stimulated [ 3 H]thymidine incorporation (ϩ35% and ϩ41%, respectively), whereas high concentrations (30 nmol/L for E 2 , 300 nmol/L for DHT) inhibited [ 3 H]thymidine incorporation (Ϫ40%). In contrast, E 2 (0.3 to 300 nmol/L) and DHT (3 to 3000 nmol/L) dose-dependently enhanced [ 3 H]thymidine incorporation in E304 cells (peak, ϩ85% for both). In VSMCs, high concentrations of E 2 and DHT inhibited platelet-derived growth factor (PDGF)-or insulin-like growth factor (IGF-1)-induced DNA synthesis (Ϫ50% to 80%), whereas PDGF-or IGF-1-dependent DNA synthesis in E304 cells was further increased by E 2 . The antiestrogens tamoxifen and raloxifene mimicked the effects of E 2 on DNA synthesis in both VSMCs and E304 cells. However, when coincubated with a stimulatory concentration of E 2 (0.3 nmol/L), tamoxifen and raloxifene blocked E 2 -induced

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Section: Discussionsupporting

confidence: 81%

Effects of Gonadal Steroids and Their Antagonists on DNA Synthesis in Human Vascular Cells

et al. 1998

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“…These results have been verified via quantitative PCR (102,103). Treatment with the ERspecific antagonist, ICI-182,780 alone (45,46), did not influence this uterine gene. However, again to our surprise, ICI-182,780 did not interfere with the induction of the LF gene by 4-OH-estradiol.…”

Section: Bodymentioning

confidence: 83%

“…This mixed agonist/antagonist function has also been reported for other compounds. The antiestrogen hydroxytamoxifen has mixed agonist/antagonist activity through ERa, depending on the tissue and gene (44,45), and can exert synergistic effects when combined with E 2 (46).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer Associated Estrogen Receptors: Catechol Estrogen Receptors in ER-Minus Mice

Lubahn¹

1999

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“…Reporter plasmid PAM119 ckb-Luc was created by cloning the 2·9 kb HindIII fragment of ckb-CAT (Somjen et al 1996) into the HindIII site of pGL3 Basic (Promega). Expression plasmids were mER -pJ3 MOR (White et al 1987), mER -pCNX2-mER (Tremblay et al 1997) and rER 2-pcDNA-ER -6 .…”

Section: Cell Culture and Transfectionsmentioning

confidence: 99%

“…The induction of ODC and CK-BB by oestradiol correlates with an increase in uterine wet weight in ovariectomised rats and provides useful markers of oestrogenicity (Olson et al 1983, Somjen et al 1996, Hibasami et al 1999. The effects of SERMs and oestradiol on the activities of these enzymes were therefore compared.…”

Section: Time-dependent Regulation Of Odc and Ck-bb By Sermsmentioning

confidence: 99%

Comparisons of the effects of tamoxifen, toremifene and raloxifene on enzyme induction and gene expression in the ovariectomised rat uterus

Green¹,

Parrott²,

Butterworth³

et al. 2001

Journal of Endocrinology

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This study compares the actions of oestradiol, tamoxifen, toremifene and raloxifene on enzyme and gene expression in uterine tissues of ovariectomised rats over 72 h. The time-course for the induction of ornithine decarboxylase by the compounds showed a rapid biphasic response, while for creatine kinase brain type (BB) there was a continued increase over 72 h. The efficacy of induction showed that, with both markers, oestradiol gave the highest induction level, followed by tamoxifen or toremifene and then raloxifene. RT-PCR demonstrated that all compounds decreased oestrogen receptor (ER) , ER and ER 2 gene expression, 8-24 h after the first dose, suggesting that down-regulation of ER is not the primary cause of the difference in efficacy between these compounds. Using cDNA arrays, expression of 512 genes was examined in the uteri of oestradiol-or tamoxifen-treated rats. Both compounds resulted in the up-regulation of heat-shock protein 27, telomerase-associated protein 1 and secretin. However, most surprising was the marked downregulation of Wilms' tumour and retinoblastoma genes. We speculate that this may result in a loss of regulation of the transition from the G1 to the S phase in the cell cycle and may make cells more vulnerable to the carcinogenic effects of tamoxifen in this tissue.

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Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo

Cited by 49 publications

References 32 publications

Effects of Gonadal Steroids and Their Antagonists on DNA Synthesis in Human Vascular Cells

Effects of Gonadal Steroids and Their Antagonists on DNA Synthesis in Human Vascular Cells

Breast Cancer Associated Estrogen Receptors: Catechol Estrogen Receptors in ER-Minus Mice

Comparisons of the effects of tamoxifen, toremifene and raloxifene on enzyme induction and gene expression in the ovariectomised rat uterus

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