TY - JOUR
T1 - Yin yang 1 plays an essential role in breast cancer and negatively regulates p27
AU - Wan, Meimei
AU - Huang, Weiwei
AU - Kute, Timothy E.
AU - Miller, Lance D.
AU - Zhang, Qiang
AU - Hatcher, Heather
AU - Wang, Jingxuan
AU - Stovall, Daniel B.
AU - Russell, Gregory B.
AU - Cao, Paul D.
AU - Deng, Zhiyong
AU - Wang, Wei
AU - Zhang, Qingyuan
AU - Lei, Ming
AU - Torti, Suzy V.
AU - Akman, Steven A.
AU - Sui, Guangchao
N1 - Funding Information:
Supported by the Golfers Against Cancer Fund, the Kulynych Interdisciplinary Cancer Research Fund, the Startup Fund of Wake Forest University School of Medicine (G.S.), and grant RSG-09-082-01-MGO from the American Cancer Society (G.S.).
PY - 2012/5
Y1 - 2012/5
N2 - Yin Yang 1 (YY1) is highly expressed in various types of cancers and regulates tumorigenesis through multiple pathways. In the present study, we evaluated YY1 expression levels in breast cancer cell lines, a breast cancer TMA, and two gene arrays. We observed that, compared with normal samples, YY1 is generally overexpressed in breast cancer cells and tissues. In functional studies, depletion of YY1 inhibited the clonogenicity, migration, invasion, and tumor formation of breast cancer cells, but did not affect the clonogenicity of nontumorigenic cells. Conversely, ectopically expressed YY1 enhanced the migration and invasion of nontumorigenic MCF-10A breast cells. In both a monolayer culture condition and a three-dimensional Matrigel system, silenced YY1 expression changed the architecture of breast cancer MCF-7 cells to that resembling MCF-10A cells, whereas ectopically expressed YY1 in MCF-10A cells had the opposite effect. Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression. Counteracting the changes in p27 expression attenuated the effects of YY1 alterations on these cells. In addition, YY1 promoted p27 ubiquitination and physically interacted with p27. In conclusion, our data suggest that YY1 is an oncogene and identify p27 as a new target of YY1.
AB - Yin Yang 1 (YY1) is highly expressed in various types of cancers and regulates tumorigenesis through multiple pathways. In the present study, we evaluated YY1 expression levels in breast cancer cell lines, a breast cancer TMA, and two gene arrays. We observed that, compared with normal samples, YY1 is generally overexpressed in breast cancer cells and tissues. In functional studies, depletion of YY1 inhibited the clonogenicity, migration, invasion, and tumor formation of breast cancer cells, but did not affect the clonogenicity of nontumorigenic cells. Conversely, ectopically expressed YY1 enhanced the migration and invasion of nontumorigenic MCF-10A breast cells. In both a monolayer culture condition and a three-dimensional Matrigel system, silenced YY1 expression changed the architecture of breast cancer MCF-7 cells to that resembling MCF-10A cells, whereas ectopically expressed YY1 in MCF-10A cells had the opposite effect. Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression. Counteracting the changes in p27 expression attenuated the effects of YY1 alterations on these cells. In addition, YY1 promoted p27 ubiquitination and physically interacted with p27. In conclusion, our data suggest that YY1 is an oncogene and identify p27 as a new target of YY1.
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U2 - 10.1016/j.ajpath.2012.01.037
DO - 10.1016/j.ajpath.2012.01.037
M3 - Article
C2 - 22440256
AN - SCOPUS:84860238252
SN - 0002-9440
VL - 180
SP - 2120
EP - 2133
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -