Knocking down cyclin D1b inhibits breast cancer cell growth and suppresses tumor development in a breast cancer model.

Abstract

Cyclin D1 is aberrantly expressed in many types of cancers, including breast cancer. High levels of cyclin D1b, the truncated isoform of cyclin D1, have been reported to be associated with a poor prognosis for breast cancer patients. In the present study, we used siRNA to target cyclin D1b overexpression and assessed its ability to suppress breast cancer growth in nude mice. Cyclin D1b siRNA effectively inhibited overexpression of cyclin D1b. Depletion of cyclin D1b promoted apoptosis of cyclin D1b-overexpressing cells and blocked their proliferation and transformation phenotypes. Notably, cyclin D1b overexpression is correlated with triple-negative basal-like breast cancers, which lack specific therapeutic targets. Administration of cyclin D1b siRNA inhibited breast tumor growth in nude mice and cyclin D1b siRNA synergistically enhanced the cell killing effects of doxorubicin in cell culture, with this combination significantly suppressing tumor growth in the mouse model. In conclusion, the results indicate that cyclin D1b, which is overexpressed in breast cancer, may serve as a novel and effective therapeutic target. More importantly, the present study clearly demonstrated a very promising therapeutic potential for cyclin D1b siRNA in the treatment of cyclin D1b-overexpressing breast cancers, including the very malignant triple-negative breast cancers.

• Authors: Min Wei, Li Zhu, Yafen Li, Weiguo Chen, Baosan Han, Zhiwei Wang, Jianrong He, Hongliang Yao, Zhongyin Yang, Qing Zhang, Bingya Liu, Qinlong Gu, Zhenggang Zhu, Kunwei Shen
• Journal: Cancer science (Cancer Sci) Vol. 102 Issue 8 Pg. 1537-44 (Aug 2011) ISSN: 1349-7006 [Electronic] England
• PMID: 21521417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• CCND1 protein, human
• Protein Isoforms
• RNA, Small Interfering
• Cyclin D1
• Doxorubicin

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (antagonists & inhibitors)
• Doxorubicin (pharmacology)
• Female
• G1 Phase
• Humans
• Mammary Neoplasms, Experimental (pathology, therapy)
• Mice
• Protein Isoforms
• RNA, Small Interfering (genetics)
• Xenograft Model Antitumor Assays