Inhibition of Estrogen Signaling Reduces the Incidence of <i>BRCA1</i>-associated Mammary Tumor Formation

Baek, Hye Jung; Kim, Sun Eui; Choi, Eun Kyung; Kim, Jong Kwang; Shin, Dong Hoon; Park, Eun Jung; Kim, Tae Hyun; Kim, Joo-Young; Kim, Kwang Gi; Deng, Chu-Xia; Kim, Sang Soo

doi:10.7150/ijbs.28142



Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

Global reach, higher impact

Full Text | PDF

Int J Biol Sci 2018; 14(12):1755-1768. doi:10.7150/ijbs.28142 This issue Cite

Research Paper

Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation

Hye Jung Baek^1*, Sun Eui Kim^1*, Eun Kyung Choi¹, Jong Kwang Kim¹, Dong Hoon Shin¹, Eun Jung Park¹, Tae Hyun Kim¹, Joo-Young Kim¹, Kwang Gi Kim², Chu-Xia Deng³, Sang Soo Kim^1✉

1. Research Institute, National Cancer Center, Goyang, 10408, Korea,
2. Department of Biomedical Engineering, Gachon University College of Medicine, Incheon, 21565, Korea,
3. Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
^*These authors contribute equally.

Citation:

Baek HJ, Kim SE, Choi EK, Kim JK, Shin DH, Park EJ, Kim TH, Kim JY, Kim KG, Deng CX, Kim SS. Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation. Int J Biol Sci 2018; 14(12):1755-1768. doi:10.7150/ijbs.28142. https://www.ijbs.com/v14p1755.htm

Other styles

Abstract

BRCA1-deficient breast cancer is a very well-known hereditary cancer. However, except for resection of normal mammary glands and ovaries, there is no acceptable measure for proactively preventing tumor development. Importantly, inherited BRCA1 mutations are closely associated with tumors in hormone-responsive tissues. Here, we examined the effects of estrogen on the accumulation of genetic instabilities upon loss of BRCA1, and assessed the contribution of estrogen signaling to the incidence and progression of Brca1-mutated mammary tumors. Our in vitro studies showed that treatment of BRCA1-depleted breast cancer cells with estrogen induced proliferation. Additionally, estrogen reduced the ability of these BRCA1-knockdown cells to sense radiation-induced DNA damage and also facilitated G1/S progression. Moreover, long-term treatment of Brca1-mutant (Brca1^co/coMMTV-Cre) mice with the selective estrogen receptor (ER)-α degrader, fulvestrant, decreased the tumor formation rate from 64% to 36%, and also significantly reduced mammary gland density in non-tumor-bearing mice. However, in vivo experiments showed that fulvestrant treatment did not alter the progression of ER-positive Brca1-mutant tumors, which were frequently identified in the aged population and showed less aggressive tendencies. These findings enhance our understanding of how ER-α signaling contributes to BRCA1-deficient mammary tumors and provide evidence suggesting that targeted inhibition of ER-α signaling may be useful for the prevention of BRCA1-mutated breast cancer.

Keywords: BRCA1, estrogen, fulvestrant, cancer prevention

Citation styles

APA

Baek, H.J., Kim, S.E., Choi, E.K., Kim, J.K., Shin, D.H., Park, E.J., Kim, T.H., Kim, J.Y., Kim, K.G., Deng, C.X., Kim, S.S. (2018). Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation. International Journal of Biological Sciences, 14(12), 1755-1768. https://doi.org/10.7150/ijbs.28142.

ACS

Baek, H.J.; Kim, S.E.; Choi, E.K.; Kim, J.K.; Shin, D.H.; Park, E.J.; Kim, T.H.; Kim, J.Y.; Kim, K.G.; Deng, C.X.; Kim, S.S. Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation. Int. J. Biol. Sci. 2018, 14 (12), 1755-1768. DOI: 10.7150/ijbs.28142.

NLM

CSE

Baek HJ, Kim SE, Choi EK, Kim JK, Shin DH, Park EJ, Kim TH, Kim JY, Kim KG, Deng CX, Kim SS. 2018. Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation. Int J Biol Sci. 14(12):1755-1768.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.