Regulation of estrogenic and nuclear factor κB functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells

Shah, Neha; Thomas, Thresia; Lewis, Joan S.; Klinge, Carolyn M.; Shirahata, Akira; Gélinas, Céline

doi:10.1038/sj.onc.1204247

Cited by 42 publications

(22 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The polyamine spermine activates NF-B in human breast cancer cells (21,22). These findings appear to be in conflict with the results reported herein.…”

Section: Discussioncontrasting

confidence: 57%

Polyamine Depletion Induces Rapid NF-κB Activation in IEC-6 Cells

Pfeffer¹,

Yang²,

Murti³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The proliferation of the rat intestinal mucosal IEC-6 cell line requires polyamines, whose synthesis is catalyzed by the enzyme ornithine decarboxylase (ODC). ODC inhibition leads to polyamine depletion, as well as inhibition of both cell proliferation and apoptosis by regulating gene expression. The NF-B transcription factor regulates genes involved in apoptotic, immune, and inflammatory responses. In the present study we tested the hypothesis that NF-B is activated following ODC inhibition. We found that the inhibition of ODC by ␣-difluoromethylornithine (DFMO) resulted in a ϳ50% decrease in intracellular putrescine levels within 1 h. NF-B is activated by DFMO through the degradation of the inhibitory protein IB␣ that sequesters NF-B in the cytoplasm. The DFMO-induced NF-B complexes contain the p65 and p50 members of the Rel protein family. DFMO-induced NF-B activation was accompanied by the translocation of p65 from the cytoplasm into the nucleus. DFMO selectively inhibited a gene reporter construct dependent on the B site present in the HLA-B7 gene. In contrast, DFMO had no effect on a gene reporter construct dependent on the B site present in the interleukin-8 gene. Thus, we report that ODC inhibition activates the NF-B transcription factor, which may mediate the altered physiological state of intestinal cells that occurs following polyamine depletion.

show abstract

“…The polyamine spermine activates NF-B in human breast cancer cells (21,22). These findings appear to be in conflict with the results reported herein.…”

Section: Discussioncontrasting

confidence: 57%

Polyamine Depletion Induces Rapid NF-κB Activation in IEC-6 Cells

Pfeffer¹,

Yang²,

Murti³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…After the specified treatments, cells were harvested and cell pellet lysed in buffer containing 50 mmol/L Tris.HCl (pH 7.4), 150 mmol/L NaCl, 1% Triton, 5 mmol/L EDTA, 25 mmol/L sodium fluoride, 25 mmol/L sodium PPi, 2 mmol/L sodium vanadate, 5% glycerol, 1 mmol/L phenylmethylsulfonyl fluoride and 1Â protease inhibitor cocktail (Calbiochem; ref. 26). Cell lysate (100 Ag in 100 AL lysis buffer) was precleared with Protein A/G agarose and incubated with 10 AL of anti-ERa (mouse monoclonal) antibody for 16 h at 4jC.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Estrogenic Effects by Beclin 1 in Breast Cancer Cells

John¹,

Nayvelt²,

Hsu

et al. 2008

Cancer Research

Self Cite

View full text Add to dashboard Cite

Beclin 1 is an essential mediator of autophagy and a regulator of cell growth and cell death. We examined the effect of Beclin 1 overexpression on the action of estradiol (E 2 ) and two antiestrogens, raloxifene and 4-hydroxytamoxifen, in estrogen receptor A (ERA)-positive MCF-7 breast cancer cells. [3 H]-thymidine incorporation studies showed that Beclin 1-overexpressing cells (MCF-7.beclin) had a lower proliferative response to E 2 compared with cells transfected with vector control (MCF-7.control). There was only a 35% increase in [ 3 H]-thymidine incorporation, after 24 hours of E 2 treatment of MCF-7.beclin cells compared with untreated cells, whereas this increase was 2-fold for MCF-7.control cells. E 2 -induced changes in the expression of early-response genes were examined by real-time quantitiative PCR. There were significant differences in the pattern of expression of E 2 -induced genes c-myc, c-fos, Erg-1, and Nur77 between MCF-7.beclin and MCF-7.control cells two hours after treatment. Although E 2 -induced growth of MCF-7.control cells was completely inhibited by 500 nmol/L raloxifene or 500 nmol/L 4-hydroxytamoxifen, these concentrations of antiestrogens had no significant effect on the growth of MCF-7.beclin cells. Confocal microscopic and coimmunoprecipitation studies showed evidence for colocalization and association of Beclin 1 and ERA. In addition, E 2 caused a decrease in Akt phosphorylation in MCF-7.beclin cells, compared with a 3-fold increase in MCF-7 cells, five minutes after treatment. These results indicate that Beclin 1 can down-regulate estrogenic signaling and growth response, and contribute to the development of antiestrogen resistance. This observation might be useful to define and overcome antiestrogen resistance of breast cancer.

show abstract

“…MCF-7 cells (1 10 5 ) were plated in 24-well microtiter plates for 24 h. By the calcium phosphate coprecipitation procedure (Mamalian Transfection Kit; Clontech, Palo Alto, CA, USA), cells were transfected with 4 µg cyclin D1 promoter plasmid linked to a firefly luciferase reporter gene and 0·4 µg Renilla luciferase plasmid (Shah et al 2001). In some experiments, cells were also transfected with 1-10 µg ATF-2 dominant negative mutant expression vector (pCMV).…”

Section: Transient Transfection Assaymentioning

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Regulation of estrogenic and nuclear factor κB functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells

Cited by 42 publications

References 98 publications

Polyamine Depletion Induces Rapid NF-κB Activation in IEC-6 Cells

Polyamine Depletion Induces Rapid NF-κB Activation in IEC-6 Cells

Regulation of Estrogenic Effects by Beclin 1 in Breast Cancer Cells

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

Contact Info

Product

Resources

About