Regulation of death promoter Bak expression by cell density and 17β-estradiol in MCF-7 cells

Leung, Lai K.; Do, Linh; Wang, Thomas T.Y.

doi:10.1016/s0304-3835(97)00430-8

Cited by 32 publications

(27 citation statements)

References 13 publications

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“…Thus, oestradiol does not appear to exert its effect on Bcl-x(L) indirectly through regulation of these growth factors. These results on Bcl-x is similar to what we have found for Bak (Leung et al, 1998) and Bcl-2 (TT Wang, unpublished observations). To determine whether the ER was necessary for oestradiol to exert its effect on Bcl-x(L), we treated cells with the anti-oestrogen tamoxifen.…”

Section: Discussionsupporting

confidence: 90%

“…The present study and our previous work (Wang and Phang, 1995;Leung et al, 1998) clearly demonstrated that oestradiol coordinately regulated the expression of several within the Bcl-2 family of proteins, and this occurs in an ER-dependent manner. This supports our hypothesis that oestradiol may regulate apoptosis through its effect on Bcl-2 family proteins.…”

Section: Discussionsupporting

confidence: 82%

“…Unexpectedly we found treatment of cells with 17β-oestradiol led to a decrease in the antiapoptotic protein Bcl-x mRNA levels ( Figure 2A). Treatment with 17β-oestradiol also leads to alteration in another Bcl-2 family proteins, Bak, which we have previously reported (Leung et al, 1998).…”

Section: Effects Of 17β-oestradiol On Bcl-2 Family Proteins' Mrna Expmentioning

confidence: 56%

“…Given the involvement of Bcl-2 family proteins in tumorigenesis (Reed, 1994;McDonnell et al, 1996;Kroemer, 1997), modulation of the Bcl-2 family anti-or pro-apoptotic proteins by oestradiol may play a critical role in the mammary carcinogenesis. Recent work has indicated a potential role for 17β-oestradiol in modulation of Bcl-2 family proteins, such as the anti-apoptotic protein Bcl-2 (Wang and Phang, 1995;Huang et al, 1997) and proapoptotic protein Bak (Leung et al, 1998). These results appear to correlate with the anti-apoptotic property of oestradiol (Kyprianou et al, 1991).…”

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confidence: 99%

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Paradoxical regulation of Bcl-2 family proteins by 17β-oestradiol in human breast cancer cells MCF-7

Leung

Wang

1999

Br J Cancer

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Summary Tumorigenesis is related to the dysregulation of cell growth or cell death pathways. Hence, elucidation of the mechanisms involved in the modulation of pro-or anti-apoptotic proteins is important in furthering understanding of breast cancer aetiology and may aid in designing prevention and treatment strategies. In the present study, we examined the role of 17β-oestradiol on the regulation of apoptosis in the breast cancer cell line MCF-7. Using multi-probe RNAase protection assays, we found changes in the mRNA levels of several Bcl-2 family proteins upon treatment of MCF-7 cells with 17β-oestradiol. Unexpectedly, we found a paradoxical effects of 17β-oestradiol on two anti-apoptotic proteins Bcl-2 and Bcl-x. Treatment with 17β-oestradiol resulted in up-regulation of Bcl-2 mRNA and protein, but down-regulated Bcl-x(L) mRNA and protein. The effect of 17β-oestradiol on Bcl-x(L) occurred at concentration-dependent fashion. The effect was specific to 17β-oestradiol since other steroid hormones exert no effect on Bcl-x(L). Tamoxifen, an anti-oestrogen, blocked the down-regulation of Bcl-x(L) by 17β-oestradiol demonstrating this effect is oestrogen receptor-dependent. We speculate that different members of the Bcl-2 family proteins may be regulated through different pathway and these pathways may be modulated by 17β-oestradiol.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 82%

Section: Effects Of 17β-oestradiol On Bcl-2 Family Proteins' Mrna Expmentioning

confidence: 56%

mentioning

confidence: 99%

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Paradoxical regulation of Bcl-2 family proteins by 17β-oestradiol in human breast cancer cells MCF-7

Leung

Wang

1999

Br J Cancer

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“…Densitometric measurements of these bands indicated a 1.5-to 3-fold increase in Bak protein levels that persisted throughout the treatment. A previous report demonstrated that Bak levels can increase with cell density in cultured cell lines, 36 and differences in Bak levels between untreated controls for the first and last timepoints were also observed in our cell lines. The same GCV-treated samples were analyzed for changes in the protein levels of the anti-apoptotic protein, Bcl-X L , by Western blot analysis (Fig 3B).…”

Section: Detection Of Apoptosis In Hsv-tk-expressing Cell Linessupporting

confidence: 83%

Two-drug combinations that increase apoptosis and modulate Bak and Bcl-XL expression in human colon tumor cell lines transduced with herpes simplex virus thymidine kinase

et al. 2000

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Herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) gene therapy can induce apoptosis in tumor cells that are normally resistant to this type of cell death, although the cellular mechanisms by which this occurs remain to be elucidated. Human colon tumor cell lines expressing HSV-TK were treated with GCV or four other inducers of apoptosis: butyrate, camptothecin (CPT), Taxol (paclitaxel), or 7-hydroxystaurosporine (UCN-01). Over a 2-4 day treatment period with GCV or the other four drugs, protein levels of the apoptosis agonist Bak increased 1.5-to 3-fold, whereas a corresponding decrease in the levels of the apoptosis antagonist, Bcl-X L , was observed in butyrate-, CPT-, and 7-hydroxystaurosporine (UCN-01)-treated cells. GCV and paclitaxel treatments resulted in increased levels of Bcl-X L . In two-drug combinations with GCV plus one of the four other drugs, increased tumor cell killing was found with GCV plus UCN-01 or with some GCV/butyrate combinations; the other two tested combinations were largely antagonistic. The GCV/UCN-01 and GCV/butyrate combinations resulted in increased Bak and decreased Bcl-X L protein levels, while the GCV/CPT and GCV/paclitaxel combinations resulted in increased levels of both proteins. The results highlight the potential for new combination therapies of HSV-TK/GCV and chemotherapeutic drugs that result in increased tumor cell apoptosis for future treatments of colon cancer.

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Conditional repression of STAT5 expression during lactation reveals its exclusive roles in mammary gland morphology, milk‐protein gene expression, and neonate growth

Reichenstein

Rauner

Barash

2011

Molecular Reproduction Devel

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The role of Stat5 in maintaining adequate lactation was studied in Stat5a(-/-) mice expressing a conditionally suppressed transgenic STAT5 in their mammary glands. This system enables distinguishing STAT5's effects on lactation from its contribution to mammary development during gestation. Females were allowed to express STAT5 during their first pregnancy. After delivery, STAT5 levels were manipulated by doxycycline administration and withdrawal. In two lines of genetically modified mice, the absence of STAT5 expression during the first 10 days of lactation resulted in a decrease of 29% or 41% in newborn weight gain. The STAT5-dependent decrease in growth was recoverable, but not completely reversible, particularly when STAT5 expression was omitted for the first 4 days of lactation. Within the first 10 days of STAT5-omitted lactation, alveolar occupancy regressed by 50% compared to that measured at delivery. By Day 10, only 18% of the fat-pad area was involved in milk production. The alveolar regression caused by 4 days of STAT5 deficiency was reversible, but neonate growth remained delayed. STAT5 deficiency resulted in reduced estrogen receptor α and connexin 32 gene expression, accompanied by delayed induction of both anti- and pro-apoptotic Bcl-2 family members. An increase in Gata-3 expression may reflect an attempt to maintain alveolar progenitors. A decrease of 39% and 23% in WAP and α-lactalbumin expression, respectively, with no associated effects on β-casein, also resulted from lack of STAT5 expression in the first 10 days of lactation. This deficiency enhances the major effect of alveolar regression on delayed weight gain in newborns.

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Regulation of death promoter Bak expression by cell density and 17β-estradiol in MCF-7 cells

Cited by 32 publications

References 13 publications

Paradoxical regulation of Bcl-2 family proteins by 17β-oestradiol in human breast cancer cells MCF-7

Paradoxical regulation of Bcl-2 family proteins by 17β-oestradiol in human breast cancer cells MCF-7

Two-drug combinations that increase apoptosis and modulate Bak and Bcl-XL expression in human colon tumor cell lines transduced with herpes simplex virus thymidine kinase

Conditional repression of STAT5 expression during lactation reveals its exclusive roles in mammary gland morphology, milk‐protein gene expression, and neonate growth

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