PMID- 20581058
OWN - NLM
STAT- MEDLINE
DCOM- 20110125
LR  - 20220317
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 177
IP  - 2
DP  - 2010 Aug
TI  - Loss of estrogen receptor 1 enhances cervical cancer invasion.
PG  - 884-95
LID - 10.2353/ajpath.2010.091166 [doi]
AB  - If left untreated, some cervical high-grade squamous intraepithelial lesions will 
      progress to invasive squamous cell carcinoma (SCC), but the molecular events 
      conferring invasive potential remain poorly defined. In prior work, we identified 
      48 genes that were down-regulated in SCCs compared with high-grade squamous 
      intraepithelial lesions and normal squamous epithelia. In this study, a 
      functional screening strategy was used to identify which of these genes regulate 
      cervical cancer cell invasion. Two independent squamous epithelial cell lines 
      were transduced with a library of short hairpin RNAs targeting the differentially 
      expressed genes and tested for invasion of the chick chorioallantoic membrane. 
      PCR was used to recover specific short hairpin RNAs from cells that invaded the 
      chorioallantoic membrane. Constructs targeting estrogen receptor 1 (ESR1) were 
      highly enriched in the invasive cells. The short hairpin RNA-mediated inhibition 
      of ESR1 in SCC- and precancer-derived cell lines increased invasiveness in both 
      in vivo and in vitro assays. Conversely, restoration of ESR1 expression in 
      ESR1-negative cervical cancer cells reduced cell invasiveness. Loss of ESR1 
      expression was found to accompany cervical cancer progression in an analysis of 
      primary normal cervix, low grade squamous intraepithelial lesions, high-grade 
      squamous intraepithelial lesions, and SCC specimens. Molecular mechanisms 
      underlying down-regulation of ESR1 in invasive cervical carcinomas appear to be 
      complex and likely heterogeneous. Our findings indicate that loss of ESR1 has a 
      major role in mediating cervical cancer invasion and progression.
FAU - Zhai, Yali
AU  - Zhai Y
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 
      48109-2200, USA.
FAU - Bommer, Guido T
AU  - Bommer GT
FAU - Feng, Ying
AU  - Feng Y
FAU - Wiese, Alexandra B
AU  - Wiese AB
FAU - Fearon, Eric R
AU  - Fearon ER
FAU - Cho, Kathleen R
AU  - Cho KR
LA  - eng
GR  - P50 CA098252/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100625
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.1.1.43 (Polycomb Repressive Complex 2)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/*genetics/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Chick Embryo
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Disease Progression
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - *Neoplasm Invasiveness
MH  - Papillomaviridae/genetics/metabolism
MH  - Polycomb Repressive Complex 2
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Uterine Cervical Neoplasms/*genetics/metabolism/*pathology
PMC - PMC2913367
EDAT- 2010/06/29 06:00
MHDA- 2011/01/28 06:00
PMCR- 2011/08/01
CRDT- 2010/06/29 06:00
PHST- 2010/06/29 06:00 [entrez]
PHST- 2010/06/29 06:00 [pubmed]
PHST- 2011/01/28 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - S0002-9440(10)60144-7 [pii]
AID - 10.2353/ajpath.2010.091166 [doi]
PST - ppublish
SO  - Am J Pathol. 2010 Aug;177(2):884-95. doi: 10.2353/ajpath.2010.091166. Epub 2010 
      Jun 25.