Tamoxifen regulates cell fate through mitochondrial estrogen receptor beta in breast cancer

Razandi, Mahnaz; Pedram, Ali; Jordan, V. Craig; Fuqua, Suzanne A.W.; Levin, Ellis R.

doi:10.1038/onc.2012.335

Cited by 75 publications

(58 citation statements)

References 52 publications

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“…With respect to differential subcellular localization of ERb-like proteins, extranuclear vs nuclear localization has been reported to provide differential prognostic information at least in breast cancer in vivo (Shaaban et al 2008. It is likely that ERb located in mitochondria and identified to interact with several mitochondrial proteins ) may have a dual role in mediating tamoxifeninduced apoptosis through increased ROS (Razandi et al 2012). This effect, seen in tamoxifen-sensitive breast cancer cell lines, did not occur in tamoxifen-resistant cells.…”

Section: Endocrine-related Cancermentioning

confidence: 79%

“…The similarity of ERb1 to ERa has led to a focus on its mechanism of action as a transcription factor and therefore on its localization to the nucleus. However, an extranuclear localization of ERb has been reported in some cells and tissues including breast cancer (Hamilton-Burke et al 2010, Leung et al 2012, Razandi et al 2012. The functions and potential mechanisms of action at the extranuclear sites are being explored.…”

Section: Endocrine-related Cancermentioning

confidence: 99%

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A bi-faceted role of estrogen receptor β in breast cancer

Leygue¹,

Murphy²

2013

Endocrine-Related Cancer

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Despite over 15 years of research, the exact role, if any, played by estrogen receptor b (ERb) in human breast cancer remains elusive. A large body of data both in vitro and in vivo supports its role as an antiproliferative, pro-apoptotic factor especially when co-expressed with ERa. However, there is a smaller body of data associating ERb with growth and survival in breast cancer. In clinical studies and most often in cell culture studies, the pro-growth and prosurvival activity of ERb occurs in ERa-negative breast cancer tissue and cells. This bi-faceted role of ERb is discussed in this review.

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Section: Endocrine-related Cancermentioning

confidence: 79%

Section: Endocrine-related Cancermentioning

confidence: 99%

A bi-faceted role of estrogen receptor β in breast cancer

Leygue¹,

Murphy²

2013

Endocrine-Related Cancer

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“…Such effects can lead to cell death and a reduction in cell viability [29] . In addition, tamoxifen rapidly inhibits estrogen-dependent protein kinase C in MCF7 cells [30] and induces rapid mitochondrial death in estrogen receptor-positive MCF7 cells [31] . In this study, a significant decrease in the mean caspase-9 activity was observed when MCF7 cells were treated with tamoxifen (10 µg/mL).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effects of tamoxifen in breast cancer cells

Hassan¹,

Jassam²,

El‐Hiti³

et al. 2018

JUMD

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Aim: To investigate the cytotoxic effects of tamoxifen on the breast cancer cell line (MCF7). Methods:The cytotoxic effects of tamoxifen on MCF7 cells were investigated using caspase-9 activity and high content screening assays. Apoptosis mechanisms following tamoxifen treatment were also investigated. Results:The most significant cytotoxic effect of tamoxifen in MCF7 cells was a half-maximal inhibitory concentration (IC 50 ) of 4.506 µg/mL. A significant increase in caspase-9 activity was also observed when MCF7 cells were treated with tamoxifen (5 µg/mL). Furthermore, increased cell membrane permeability, cytochrome c level, and nuclear intensity were observed with tamoxifen (100 µg/mL) compared with doxorubicin (20 µg/mL) treatment. However, a noticeable decrease in cell viability and mitochondrial membrane permeability was observed with tamoxifen (100 µg/mL) treatment compared with doxorubicin (20 µg/mL) as a positive control. Conclusion:Tamoxifen showed in vitro cytotoxic effects in MCF7 cells as demonstrated by high-content screening and caspase-9 activity assays. Tamoxifen inhibits estrogen mechanisms, although toxic effect was observed.

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“…Studies over the past decade have clearly demonstrated a role for ERs residing near or in the plasma membrane and a role for ER in the mitochondria (Pietras & Szego 1977, Selvaraj et al 2000, Watters et al 2000, Song et al 2004, Yang et al 2004, Dahlman-Wright et al 2006, Song 2007, Yager & Chen 2007, Madak-Erdogan et al 2008, Haas et al 2009, Pedram et al 2009, Wu et al 2011, Razandi et al 2013, Levin 2014a,b, 2015, Marjon et al 2014. Cytosolic ER is palmitoylated, which allows localization in or near the plasma membrane.…”

Section: Membrane Initiated Oestrogen Effectsmentioning

confidence: 99%

“…Several investigators have suggested that mitochondrial ERb can enhance cell survival. A recent study suggests that tamoxifen influences the process of apoptosis through interactions with ERb in breast cancer cells (Razandi et al 2013). Tamoxifen, acting either as an antagonist or agonist, differentially regulates manganese superoxide dismutase that impacts reactive oxygen species levels.…”

Section: Vascular Endothelial Cellsmentioning

confidence: 99%

Celebrating 75 years of oestradiol

Simpson

Santen

2015

Journal of Molecular Endocrinology

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Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story. Two investigators, Edward Doisy and Alfred Butenandt, purified and crystalized oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await his purification of vitamin K. Early investigators quickly recognized that oestrogens must be synthesized from androgens and later investigators called this process aromatization. The aromatase enzyme was then characterized, its mechanism determined, and its structure identified after successful crystallization. With the development of knock-out methodology, the precise effects of oestrogen in males and females were defined and clinical syndromes of deficiency and excess described. Their discovery ultimately led to the development of oral contraceptives, treatment of menopausal symptoms, therapies for breast cancer, and induction of fertility, among others. The history of the use of oestrogens for postmenopausal women to relieve symptoms has been characterized by cyclic periods of enthusiasm and concern. The individuals involved in these studies, the innovative thinking required, and the detailed understanding made possible by evolving biologic and molecular techniques provide many lessons for current endocrinologists. Discovery of oestrogenThe concept that substances secreted by one organ could then be transported internally to another via the blood stream is the underpinning of the field of endocrinology. The 'father of physiology', Claude Bernard, articulated the concept of internal secretion by describing how the liver produces glucose, which then travels to and is utilized by other tissues in the body. This concept underlies studies on the ovaries, which became a focus of investigation later in the century. In 1896, Emil Knauer, a 29-year-old Austrian, excised the ovaries of adult rabbits and then re-implanted pieces into different locations in the same animals (Watkins 2007 Doisy then enlisted a nurse in the obstetrics clinic to supply each pregnant patient with a 1 gal jug and ask for her urine. This provided the needed material but was fraught with difficulties. Suspected to be a bootlegger because of the large jugs of yellow material in his car, one of Doisy's drivers was nearly arrested until he suggested using the sniff test with the response 'My god, it is urine'. Doisy, then being recruited to St Louis University, continued his efforts to purify the active substance. Each extract was tested with a bioassay and its effect on uterine stimulation. Urine, the material of choice for study, was initially extracted with a very large countercurrent apparatus (Fig. 1). Costing the exorbitan...

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Tamoxifen regulates cell fate through mitochondrial estrogen receptor beta in breast cancer

Cited by 75 publications

References 52 publications

A bi-faceted role of estrogen receptor β in breast cancer

A bi-faceted role of estrogen receptor β in breast cancer

Cytotoxic effects of tamoxifen in breast cancer cells

Celebrating 75 years of oestradiol

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