title: Yin Yang 1 plays an essential role in breast cancer and negatively regulates p27.
abstract: 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.
authors.affiliation: Comprehensive Cancer Center Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Meimei
authors.initials: M
authors.lastname: Wan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kute
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Heather
authors.initials: H
authors.lastname: Hatcher
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Wang
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Stovall
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Russell
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Suzy V
authors.initials: SV
authors.lastname: Torti
authors.forename: Steven A
authors.initials: SA
authors.lastname: Akman
authors.forename: Guangchao
authors.initials: G
authors.lastname: Sui
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D048430:Cell Shape / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C413374:p27 antigen