Estrogens and cell-cycle regulation in breast cancer

Foster, James S.; Henley, Donald C.; Ahamed, Shamila; Wimalasena, Jay

doi:10.1016/s1043-2760(01)00436-2

Cited by 191 publications

(154 citation statements)

References 75 publications

Supporting

Mentioning

144

Contrasting

Unclassified

Order By: Relevance

“…As expected, another Akt activator IGF-1 also completely inhibited GSK3␤ activity. The effect of E 2 was sustained for 60 min (our unpublished data), and such a time course is compatible with the increase in cyclin D1 protein observed 3-4 h after E 2 addition to quiescent cells (Foster and Wimalasena, 1996;Foster et al, 2001). …”

Section: Estradiol Activates the Pi-3k/akt Pathway Leading To Phosphsupporting

confidence: 79%

“…Previous studies in our laboratory had demonstrated that E 2 induced p27 kip1 degradation and entry of quiescent MCF7 cells to the cell cycle requires Ras activity (Ahamed et al, , 2002Foster et al, 2001). Other investigators have demonstrated that E 2 rapidly activated Ras in MCF7 cells (Keshamouni et al, 2002), and recent work in our laboratory (Foster, 2003) demonstrated that Ras activity is required for nuclear export and degradation of p27 kip1 in response to E 2 .…”

Section: Estradiol-induced Bad Phosphorylation Requires Rasactivated mentioning

confidence: 86%

See 1 more Smart Citation

Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

Fernando

Wimalasena

2004

MBoC

Self Cite

113

View full text Add to dashboard Cite

Estrogens such as 17-β estradiol (E2) play a critical role in sporadic breast cancer progression and decrease apoptosis in breast cancer cells. Our studies using estrogen receptor-positive MCF7 cells show that E2 abrogates apoptosis possibly through phosphorylation/inactivation of the proapoptotic protein BAD, which was rapidly phosphorylated at S112 and S136. Inhibition of BAD protein expression with specific antisense oligonucleotides reduced the effectiveness of tumor necrosis factor-α, H2O2, and serum starvation in causing apoptosis. Furthermore, the ability of E2 to prevent tumor necrosis factor-α-induced apoptosis was blocked by overexpression of the BAD S112A/S136A mutant but not the wild-type BAD. BAD S112A/S136A, which lacks phosphorylation sites for p90RSK1 and Akt, was not phosphorylated in response to E2 in vitro. E2 treatment rapidly activated phosphatidylinositol 3-kinase (PI-3K)/Akt and p90RSK1 to an extent similar to insulin-like growth factor-1 treatment. In agreement with p90RSK1 activation, E2 also rapidly activated extracellular signal-regulated kinase, and this activity was down-regulated by chemical and biological inhibition of PI-3K suggestive of cross talk between signaling pathways responding to E2. Dominant negative Ras blocked E2-induced BAD phosphorylation and the Raf-activator RasV12T35S induced BAD phosphorylation as well as enhanced E2-induced phosphorylation at S112. Chemical inhibition of PI-3K and mitogen-activated protein kinase kinase 1 inhibited E2-induced BAD phosphorylation at S112 and S136 and expression of dominant negative Ras-induced apoptosis in proliferating cells. Together, these data demonstrate a new nongenomic mechanism by which E2 prevents apoptosis.

show abstract

Section: Estradiol Activates the Pi-3k/akt Pathway Leading To Phosphsupporting

confidence: 79%

Section: Estradiol-induced Bad Phosphorylation Requires Rasactivated mentioning

confidence: 86%

Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

Fernando

Wimalasena

2004

MBoC

Self Cite

113

View full text Add to dashboard Cite

show abstract

“…E2 has been shown to elicit pleiotropic effects, including cell cycle regulation (Foster et al, 2001) and ROS generation, through oxidative metabolism or by acting on mitochondrial uncoupling proteins (Fussell et al, 2011). To evaluate whether NRF2 accumulation was caused by E2-induced ROS increase, we measured ROS levels in MCF7 at 4 h after treatment with 10 nM E2, but we did not detect any changes in ROS levels between E2-treated cells and control cells (Fig.…”

Section: Brca1-deficient Pmecs Have a Limited Lifespan In Vivomentioning

confidence: 92%

BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival

Gorrini¹,

Baniasadi²,

Harris³

et al. 2013

J Cell Biol

View full text Add to dashboard Cite

Oxidative stress plays an important role in cancer development and treatment. Recent data implicate the tumor suppressor BRCA1 in regulating oxidative stress, but the molecular mechanism and the impact in BRCA1-associated tumorigenesis remain unclear. Here, we show that BRCA1 regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 and promoting its stability and activation. BRCA1-deficient mouse primary mammary epithelial cells show low expression of Nrf2-regulated antioxidant enzymes and accumulate reactive oxygen species (ROS) that impair survival in vivo. Increased Nrf2 activation rescues survival and ROS levels in BRCA1-null cells. Interestingly, 53BP1 inactivation, which has been shown to alleviate several defects associated with BRCA1 loss, rescues survival of BRCA1-null cells without restoring ROS levels. We demonstrate that estrogen treatment partially restores Nrf2 levels in the absence of BRCA1. Our data suggest that Nrf2-regulated antioxidant response plays a crucial role in controlling survival downstream of BRCA1 loss. The ability of estrogen to induce Nrf2 posits an involvement of an estrogen-Nrf2 connection in BRCA1 tumor suppression. Lastly, BRCA1-mutated tumors retain a defective antioxidant response that increases the sensitivity to oxidative stress. In conclusion, the role of BRCA1 in regulating Nrf2 activity suggests important implications for both the etiology and treatment of BRCA1-related cancers.

show abstract

“…One commonly used cell line whose growth is stimulated by E2 is the ER␣-positive cell line T47D (3,4). E2 regulates expression of key cell-cycle genes such as c-Myc, cyclin D1, cyclin E, A, Cdc25A, p45 Skip2 , and p27 Kip1 (5)(6)(7)(8)(9)(10). The cyclin D promoter is one site where ER␤ opposes ER␣-mediated activation and the ER␤-antiestrogen complex can stimulate transcription (1).…”

Section: Estrogen Receptor ␤ Inhibits 17␤-estradiol-stimulated Prolifmentioning

confidence: 99%

Estrogen receptor β inhibits 17β-estradiol-stimulated proliferation of the breast cancer cell line T47D

Ström

Hartman

Foster

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

501

392

View full text Add to dashboard Cite

Estrogen receptor (ER) β counteracts the activity of ERα in many systems. In agreement with this, we show in this study that induced expression of ERβ in the breast cancer cell line T47D reduces 17β-estradiol-stimulated proliferation when expression of ERβ mRNA equals that of ERα. Induction of ERβ reduces growth of exponentially proliferating cells with a concomitant decrease in components of the cell cycle associated with proliferation, namely cyclin E, Cdc25A (a key regulator of Cdk2), p45 Skp2 (a key regulator of p27 Kip1 proteolysis), and an increase in the Cdk inhibitor p27 Kip1 . We also observed a reduced Cdk2 activity. These findings suggest a possible role for ERβ in breast cancer and imply that ERβ-specific ligands may reduce proliferation of ER-positive breast cancer cells through actions on the G 1 phase cell-cycle machinery.

show abstract

Estrogens and cell-cycle regulation in breast cancer

Cited by 191 publications

References 75 publications

Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt

BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival

Estrogen receptor β inhibits 17β-estradiol-stimulated proliferation of the breast cancer cell line T47D

Contact Info

Product

Resources

About