J Cancer 2014; 5(5):336-343. doi:10.7150/jca.7202 This issue Cite

Research Paper

Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transforming Growth Factor-β Signaling via Estrogen Receptor α

Natsuka Goto1*, Hiromi Hiyoshi1,2*✉, Ichiaki Ito1, Keisuke Iida 3, Yuka Nakajima1,2, Kazuo Nagasawa3, Junn Yanagisawa1,2✉

1. Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
2. Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
3. Faculty of Technology, Tokyo University of Agriculture and Technology-TUAT, 2-24-16 Naka-cho, Koganei-shi, Tokyo 185-0031, Japan.
* equal contribution.

Citation:
Goto N, Hiyoshi H, Ito I, Iida K, Nakajima Y, Nagasawa K, Yanagisawa J. Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transforming Growth Factor-β Signaling via Estrogen Receptor α. J Cancer 2014; 5(5):336-343. doi:10.7150/jca.7202. https://www.jcancer.org/v05p0336.htm
Other styles

File import instruction

Abstract

Breast cancer is the most frequently diagnosed cancer and the leading cause of death by cancer among females worldwide. An overwhelming majority of these deaths is because of metastasis. Estrogen stimulates and promotes growth of breast tumors, whereas transforming growth factor-beta (TGF-β) signaling promotes invasion and metastasis. We previously reported that estrogen and estrogen receptor alpha (ERα) suppressed breast cancer metastasis by inhibiting TGF-β signaling, whereas antiestrogens that suppress breast cancer growth, such as the selective ER modulator tamoxifen (TAM) or the pure antiestrogen fulvestrant (ICI 182,780), cannot suppress TGF-β signaling or breast cancer invasiveness. Therefore, we predicted that a compound that inhibits TGF-β signaling but does not facilitate ERα signaling would be ideal for suppressing breast cancer invasiveness and growth. In the present study, we identified an ideal candidate compound, N-23. Like estrogen, N-23 strongly decreased expression of TGF-β/Smad target gene plasminogen activator inhibitor-1 (PAI-1), but it did not increase the expression of ERα target gene pS2. While estrogen decreased the levels of phosphorylated Smad2 and Smad3, N-23 had no effect. In addition, TGF-β-dependent recruitment of Smad3 to the PAI-1 gene promoter was inhibited in the presence of estrogen or N-23. We also investigated the effects of N-23 on proliferation, migration, and invasion of breast cancer cells. In contrast to estrogen, N-23 inhibited the cellular proliferation of breast cancer cells. Moreover, we showed that N-23 suppressed the migration and invasion of breast cancer cells to the same extent as by estrogen. Taken together, our findings indicate that N-23 may be a candidate compound that is effective in inhibiting breast cancer progression.

Keywords: TGF-β, ERα, breast cancer, compounds, invasion and metastasis.


Citation styles

APA
Goto, N., Hiyoshi, H., Ito, I., Iida, K., Nakajima, Y., Nagasawa, K., Yanagisawa, J. (2014). Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transforming Growth Factor-β Signaling via Estrogen Receptor α. Journal of Cancer, 5(5), 336-343. https://doi.org/10.7150/jca.7202.

ACS
Goto, N.; Hiyoshi, H.; Ito, I.; Iida, K.; Nakajima, Y.; Nagasawa, K.; Yanagisawa, J. Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transforming Growth Factor-β Signaling via Estrogen Receptor α. J. Cancer 2014, 5 (5), 336-343. DOI: 10.7150/jca.7202.

NLM
Goto N, Hiyoshi H, Ito I, Iida K, Nakajima Y, Nagasawa K, Yanagisawa J. Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transforming Growth Factor-β Signaling via Estrogen Receptor α. J Cancer 2014; 5(5):336-343. doi:10.7150/jca.7202. https://www.jcancer.org/v05p0336.htm

CSE
Goto N, Hiyoshi H, Ito I, Iida K, Nakajima Y, Nagasawa K, Yanagisawa J. 2014. Identification of a Novel Compound That Suppresses Breast Cancer Invasiveness by Inhibiting Transforming Growth Factor-β Signaling via Estrogen Receptor α. J Cancer. 5(5):336-343.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image