PMID- 21276249
OWN - NLM
STAT- MEDLINE
DCOM- 20140325
LR  - 20220410
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 13
IP  - 1
DP  - 2011 Jan 28
TI  - Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal 
      breast cancer.
PG  - R11
LID - 10.1186/bcr2819 [doi]
AB  - INTRODUCTION: Tumors that express estrogen receptor alpha (ERalpha+) comprise 75% of 
      breast cancers in women. While treatments directed against this receptor have 
      successfully lowered mortality rates, many primary tumors initially or later 
      exhibit resistance. The paucity of murine models of this "luminal" tumor subtype 
      has hindered studies of factors that promote their pathogenesis and modulate 
      responsiveness to estrogen-directed therapeutics. Since epidemiologic studies 
      closely link prolactin and the development of ERalpha+ tumors in women, we examined 
      characteristics of the aggressive ERalpha+ and ERalpha- carcinomas which develop in 
      response to mammary prolactin in a murine transgenic model (neu-related 
      lipocalin- prolactin (NRL-PRL)). To evaluate their relationship to clinical 
      tumors, we determined phenotypic relationships among these carcinomas, other 
      murine models of breast cancer, and features of luminal tumors in women. METHODS: 
      We examined a panel of prolactin-induced tumors for characteristics relevant to 
      clinical tumors: histotype, ERalpha/progesterone receptor (PR) expression and 
      estrogen responsiveness, Activating Protein 1 (AP-1) components, and 
      phosphorylation of signal transducer and activator of transcription 5 (Stat5), 
      extracellular signal regulated kinase (ERK) 1/2 and AKT. We compared levels of 
      transcripts in the ERalpha-associated "luminal" signature that defines this subtype 
      of tumors in women and transcripts enriched in various mammary epithelial 
      lineages to other well-studied genetically modified murine models of breast 
      cancer. Finally, we used microarray analyses to compare prolactin-induced ERalpha+ 
      and ERalpha- tumors, and examined responsiveness to estrogen and the anti-estrogen, 
      Faslodex, in vivo. RESULTS: Prolactin-induced carcinomas were markedly diverse 
      with respect to histotype, ERalpha/PR expression, and activated signaling cascades. 
      They constituted a heterogeneous, but distinct group of murine mammary tumors, 
      with molecular features of the luminal subtype of human breast cancer. In 
      contrast to morphologically normal and hyperplastic structures in NRL-PRL 
      females, carcinomas were insensitive to ERalpha-mediated signals. These tumors were 
      distinct from mouse mammary tumor virus (MMTV)-neu tumors, and contained elevated 
      transcripts for factors associated with luminal/alveolar expansion and 
      differentiation, suggesting that they arose from physiologic targets of 
      prolactin. These features were shared by ERalpha+ and ERalpha- tumors, suggesting a 
      common origin, although the former exhibited transcript profiles reflecting 
      greater differentiation. CONCLUSIONS: Our studies demonstrate that prolactin can 
      promote diverse carcinomas in mice, many of which resemble luminal breast 
      cancers, providing a novel experimental model to examine the pathogenesis, 
      progression and treatment responsiveness of this tumor subtype.
FAU - Arendt, Lisa M
AU  - Arendt LM
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 
      Linden Dr., Madison, WI 53706, USA.
FAU - Rugowski, Debra E
AU  - Rugowski DE
FAU - Grafwallner-Huseth, Tara A
AU  - Grafwallner-Huseth TA
FAU - Garcia-Barchino, Maria Jose
AU  - Garcia-Barchino MJ
FAU - Rui, Hallgeir
AU  - Rui H
FAU - Schuler, Linda A
AU  - Schuler LA
LA  - eng
GR  - R01 CA78312/CA/NCI NIH HHS/United States
GR  - R01 CA118740/CA/NCI NIH HHS/United States
GR  - K01 RR021858/RR/NCRR NIH HHS/United States
GR  - T32 AG00265/AG/NIA NIH HHS/United States
GR  - DK62783/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110128
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Transcription Factor AP-1)
RN  - 9002-62-4 (Prolactin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/genetics
MH  - Breast Neoplasms/genetics/*metabolism
MH  - Carcinoma/genetics/*metabolism
MH  - Cluster Analysis
MH  - Disease Models, Animal
MH  - Epithelial Cells/metabolism
MH  - Estrogen Receptor alpha/genetics/metabolism
MH  - Estrogens/*physiology
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Male
MH  - Mammary Neoplasms, Experimental/etiology/genetics/*metabolism
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Prolactin/*genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT5 Transcription Factor/metabolism
MH  - Transcription Factor AP-1/metabolism
PMC - PMC3109579
EDAT- 2011/02/01 06:00
MHDA- 2014/03/26 06:00
PMCR- 2011/01/28
CRDT- 2011/02/01 06:00
PHST- 2010/09/05 00:00 [received]
PHST- 2010/11/30 00:00 [revised]
PHST- 2011/01/28 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2014/03/26 06:00 [medline]
PHST- 2011/01/28 00:00 [pmc-release]
AID - bcr2819 [pii]
AID - 10.1186/bcr2819 [doi]
PST - epublish
SO  - Breast Cancer Res. 2011 Jan 28;13(1):R11. doi: 10.1186/bcr2819.