PMID- 25633981
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20210103
IS  - 1754-8411 (Electronic)
IS  - 1754-8403 (Print)
IS  - 1754-8403 (Linking)
VI  - 8
IP  - 3
DP  - 2015 Mar
TI  - Functional and molecular characterisation of EO771.LMB tumours, a new 
      C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer.
PG  - 237-51
LID - 10.1242/dmm.017830 [doi]
AB  - The translation of basic research into improved therapies for breast cancer 
      patients requires relevant preclinical models that incorporate spontaneous 
      metastasis. We have completed a functional and molecular characterisation of a 
      new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and 
      contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB 
      tumours were derived from poorly metastatic parental EO771 mammary tumours. 
      Functional differences were evaluated using both in vitro assays and spontaneous 
      metastasis assays in mice. Results were compared to non-metastatic 67NR and 
      metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of 
      markers of human breast cancer molecular subtypes were measured in the four 
      tumour lines, as well as p53 (Tp53) tumour-suppressor gene status and responses 
      to tamoxifen in vivo and in vitro. Array-based expression profiling of whole 
      tumours identified genes and pathways that were deregulated in metastatic 
      tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and 
      displayed increased invasive capacity compared with parental EO771. By 
      immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 
      4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all 
      lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, 
      but positive for epidermal growth factor receptor (EGFR). Only 67NR displayed 
      nuclear estrogen receptor alpha (ERalpha) positivity. EO771 and EO771.LMB expressed 
      mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis 
      of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of 
      matrix metalloproteinase-3 (MMP-3), parathyroid hormone-like hormone (Pthlh) and 
      S100 calcium binding protein A8 (S100a8) and downregulation of the thrombospondin 
      receptor (Cd36) might be causally involved in metastatic dissemination of breast 
      cancer.
CI  - (c) 2015. Published by The Company of Biologists Ltd.
FAU - Johnstone, Cameron N
AU  - Johnstone CN
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia Sir Peter MacCallum Department of Oncology, 
      University of Melbourne, Parkville, VIC 3010, Australia Department of Pathology, 
      University of Melbourne, Parkville, VIC 3010, Australia Department of 
      Pharmacology & Therapeutics, University of Melbourne, Parkville, VIC 3010, 
      Australia.
FAU - Smith, Yvonne E
AU  - Smith YE
AD  - Angiogenesis and Metastasis Research, Royal College of Surgeons in Ireland, 123 
      St Stephen's Green, Dublin 2, Ireland.
FAU - Cao, Yuan
AU  - Cao Y
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Burrows, Allan D
AU  - Burrows AD
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Cross, Ryan S N
AU  - Cross RS
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Ling, Xiawei
AU  - Ling X
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Redvers, Richard P
AU  - Redvers RP
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Doherty, Judy P
AU  - Doherty JP
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Eckhardt, Bedrich L
AU  - Eckhardt BL
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia Morgan Welch Inflammatory Breast Cancer Research 
      and Clinic, Department of Breast Medical Oncology, The University of Texas, MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Natoli, Anthony L
AU  - Natoli AL
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Restall, Christina M
AU  - Restall CM
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Lucas, Erin
AU  - Lucas E
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Pearson, Helen B
AU  - Pearson HB
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Deb, Siddhartha
AU  - Deb S
AD  - Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, VIC 
      2010, Australia.
FAU - Britt, Kara L
AU  - Britt KL
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia Sir Peter MacCallum Department of Oncology, 
      University of Melbourne, Parkville, VIC 3010, Australia.
FAU - Rizzitelli, Alexandra
AU  - Rizzitelli A
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Li, Jason
AU  - Li J
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia.
FAU - Harmey, Judith H
AU  - Harmey JH
AD  - Angiogenesis and Metastasis Research, Royal College of Surgeons in Ireland, 123 
      St Stephen's Green, Dublin 2, Ireland.
FAU - Pouliot, Normand
AU  - Pouliot N
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia Sir Peter MacCallum Department of Oncology, 
      University of Melbourne, Parkville, VIC 3010, Australia Department of Pathology, 
      University of Melbourne, Parkville, VIC 3010, Australia 
      normand.pouliot@petermac.org robin.anderson@petermac.org.
FAU - Anderson, Robin L
AU  - Anderson RL
AD  - Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East 
      Melbourne, VIC 3002, Australia Sir Peter MacCallum Department of Oncology, 
      University of Melbourne, Parkville, VIC 3010, Australia Department of Pathology, 
      University of Melbourne, Parkville, VIC 3010, Australia 
      normand.pouliot@petermac.org robin.anderson@petermac.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150129
PL  - England
TA  - Dis Model Mech
JT  - Disease models & mechanisms
JID - 101483332
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 094ZI81Y45 (Tamoxifen)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/metabolism
MH  - Cell Line, Tumor
MH  - *Disease Models, Animal
MH  - Estrogen Receptor alpha/antagonists & inhibitors/genetics/metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Mammary Neoplasms, Animal/classification/drug therapy/genetics/*pathology
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neoplasm Metastasis/genetics/*pathology
MH  - Neoplasm Proteins/metabolism
MH  - Phenotype
MH  - RNA, Messenger/genetics/metabolism
MH  - Tamoxifen/pharmacology/therapeutic use
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC4348562
OTO - NOTNLM
OT  - Breast cancer
OT  - Estrogen receptor alpha
OT  - Metastasis
OT  - Syngeneic preclinical models
OT  - Tumour subtyping
EDAT- 2015/01/31 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/03/01
CRDT- 2015/01/31 06:00
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - dmm.017830 [pii]
AID - 0080237 [pii]
AID - 10.1242/dmm.017830 [doi]
PST - ppublish
SO  - Dis Model Mech. 2015 Mar;8(3):237-51. doi: 10.1242/dmm.017830. Epub 2015 Jan 29.