PMID- 15535849
OWN - NLM
STAT- MEDLINE
DCOM- 20050414
LR  - 20220310
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 6
IP  - 6
DP  - 2004
TI  - Proteotypic classification of spontaneous and transgenic mammary neoplasms.
PG  - R668-79
AB  - INTRODUCTION: Mammary tumors in mice are categorized by using morphologic and 
      architectural criteria. Immunolabeling for terminal differentiation markers was 
      compared among a variety of mouse mammary neoplasms because expression of 
      terminal differentiation markers, and especially of keratins, provides important 
      information on the origin of neoplastic cells and their degree of 
      differentiation. METHODS: Expression patterns for terminal differentiation 
      markers were used to characterize tumor types and to study tumor progression in 
      transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), 
      Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, 
      and in mammary neoplasms associated with infection by the mouse mammary tumor 
      virus (MMTV). RESULTS: On the basis of the expression of terminal differentiation 
      markers, three types of neoplasm were identified: first, simple carcinomas 
      composed exclusively of cells with a luminal phenotype are characteristic of 
      neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; 
      second, 'complex carcinomas' displaying luminal and myoepithelial differentiation 
      are characteristic of type P tumors arising in mice transgenic for Wnt1, 
      neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous 
      carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition 
      (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and 
      SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display 
      de novo expression of myoepithelial and mesenchymal cell markers. In sharp 
      contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ 
      mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or 
      in neoplasms arising in mice transgenic for Neu and Wnt1. CONCLUSIONS: 
      Immunohistochemical profiles of complex neoplasms are consistent with a stem cell 
      origin, whereas simple carcinomas might originate from a cell committed to the 
      luminal lineage. In addition, these results suggest that the initiating oncogenic 
      events determine the morphologic features associated with cancer progression 
      because EMT is observed only in certain types of neoplasm.
FAU - Mikaelian, Igor
AU  - Mikaelian I
AD  - The Jackson Laboratory, Bar Harbor, Maine, USA. igor.mikaelian@roche.com
FAU - Blades, Natalie
AU  - Blades N
FAU - Churchill, Gary A
AU  - Churchill GA
FAU - Fancher, Karen
AU  - Fancher K
FAU - Knowles, Barbara B
AU  - Knowles BB
FAU - Eppig, Janan T
AU  - Eppig JT
FAU - Sundberg, John P
AU  - Sundberg JP
LA  - eng
GR  - R33 CA088327/CA/NCI NIH HHS/United States
GR  - CA88327/CA/NCI NIH HHS/United States
GR  - R01 CA089713/CA/NCI NIH HHS/United States
GR  - P30 CA034196/CA/NCI NIH HHS/United States
GR  - R21 CA088327/CA/NCI NIH HHS/United States
GR  - CA89713/CA/NCI NIH HHS/United States
GR  - CA34196/CA/NCI NIH HHS/United States
GR  - RR173/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041006
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Myc protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt1 Protein)
RN  - 0 (Wnt1 protein, mouse)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/*biosynthesis/genetics
MH  - Carcinoma/classification/genetics/metabolism/pathology
MH  - Cell Differentiation/physiology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Epithelial Cells/pathology
MH  - Female
MH  - Immunohistochemistry
MH  - Intercellular Signaling Peptides and Proteins/genetics
MH  - Keratins/biosynthesis/genetics
MH  - Mammary Neoplasms, Experimental/*classification/genetics/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Transgenic
MH  - Proteomics/methods
MH  - Proto-Oncogene Proteins c-myc/biosynthesis/genetics
MH  - Wnt Proteins
MH  - Wnt1 Protein
PMC - PMC1064077
EDAT- 2004/11/13 09:00
MHDA- 2005/04/15 09:00
PMCR- 2004/10/06
CRDT- 2004/11/13 09:00
PHST- 2004/05/26 00:00 [received]
PHST- 2004/07/16 00:00 [revised]
PHST- 2004/08/09 00:00 [accepted]
PHST- 2004/11/13 09:00 [pubmed]
PHST- 2005/04/15 09:00 [medline]
PHST- 2004/11/13 09:00 [entrez]
PHST- 2004/10/06 00:00 [pmc-release]
AID - bcr930 [pii]
AID - 10.1186/bcr930 [doi]
PST - ppublish
SO  - Breast Cancer Res. 2004;6(6):R668-79. doi: 10.1186/bcr930. Epub 2004 Oct 6.