PMID- 15750629
OWN - NLM
STAT- MEDLINE
DCOM- 20050630
LR  - 20221003
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 22
DP  - 2005 May 19
TI  - Promotion of mammary cancer development by tamoxifen in a mouse model of 
      Brca1-mutation-related breast cancer.
PG  - 3554-62
AB  - Loss of full-length Brca1 in mammary epithelial cells of the mouse mammary tumor 
      virus (MMTV)-Cre Brca1 conditional exon 11 deletion mouse model results in the 
      development of mammary adenocarcinomas with similar genetic changes to those 
      found in human BRCA1-mutation-related breast cancers. We used this experimental 
      model to evaluate the chemopreventive effect of tamoxifen on the development of 
      mammary preneoplasia and adenocarcinoma. No protective effects of tamoxifen 
      administration on mammary cancer development were found. Instead, tamoxifen 
      treatment significantly increased rates of mammary epithelial cell proliferation 
      and the prevalence of mammary hyperplasia at 6 months of age. Tamoxifen-exposed 
      mice developed adenocarcinomas at younger ages than control mice and a higher 
      percentage of mice developed adenocarcinomas by 12 months of age. Both whole 
      mouse and tissue culture cell models were used to test if loss of full-length 
      Brca1 was associated with a relative increase in the agonist activity of 
      tamoxifen. Tamoxifen induced increased ductal growth in MMTV-Cre Brca1 
      conditional mice compared to wild type. Estrogen receptor alpha (ERalpha) 
      expression was downregulated in the tamoxifen-induced hyperplasias. Reducing 
      BRCA1 levels in MCF-7 cells using siRNA resulted in a relative increase in the 
      agonist activity of tamoxifen. Results suggest a model of mammary cancer 
      progression in which loss of full-length Brca1 altered the agonist/antagonist 
      activity of tamoxifen, resulting in tamoxifen-induced mammary epithelial cell 
      proliferation with subsequent loss of ERalpha expression and development of 
      ERalpha-negative hyperplasias and adenocarcinomas.
FAU - Jones, Laundette P
AU  - Jones LP
AD  - Department of Oncology, Lombardi Cancer Center, Georgetown University, 
      Washington, DC 20057, USA.
FAU - Li, Minglin
AU  - Li M
FAU - Halama, Ewa D
AU  - Halama ED
FAU - Ma, Yongxian
AU  - Ma Y
FAU - Lubet, Ronald
AU  - Lubet R
FAU - Grubbs, Clinton J
AU  - Grubbs CJ
FAU - Deng, Chu-Xia
AU  - Deng CX
FAU - Rosen, Eliot M
AU  - Rosen EM
FAU - Furth, Priscilla A
AU  - Furth PA
LA  - eng
GR  - T32 CA009686/CA/NCI NIH HHS/United States
GR  - N01-CN-05024/CN/NCI NIH HHS/United States
GR  - 2T32CA09-686-08/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (BRCA1 Protein)
RN  - 0 (Estrogen Receptor alpha)
RN  - 094ZI81Y45 (Tamoxifen)
SB  - IM
MH  - Adenocarcinoma/genetics/*pathology
MH  - Animals
MH  - Antineoplastic Agents, Hormonal/*adverse effects
MH  - Apoptosis/drug effects
MH  - BRCA1 Protein/*drug effects
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Epithelial Cells/drug effects
MH  - Estrogen Receptor alpha/drug effects
MH  - Female
MH  - Humans
MH  - Hyperplasia/genetics
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Mammary Neoplasms, Experimental/genetics/*pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tamoxifen/*adverse effects
EDAT- 2005/03/08 09:00
MHDA- 2005/07/01 09:00
CRDT- 2005/03/08 09:00
PHST- 2005/03/08 09:00 [pubmed]
PHST- 2005/07/01 09:00 [medline]
PHST- 2005/03/08 09:00 [entrez]
AID - 1208426 [pii]
AID - 10.1038/sj.onc.1208426 [doi]
PST - ppublish
SO  - Oncogene. 2005 May 19;24(22):3554-62. doi: 10.1038/sj.onc.1208426.