Transcription factors link mouse WAP-T mammary tumors with human breast cancer
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Transcription factors link mouse WAP-T mammary tumors with human breast cancer. / Otto, Benjamin; Streichert, Thomas; Wegwitz, Florian; Gevensleben, Heidrun; Klätschke, Kristin; Wagener, Christoph; Deppert, Wolfgang; Tolstonog, Genrich V.
in: INT J CANCER, Jahrgang 132, Nr. 6, 6, 15.03.2013, S. 1311-1322.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Transcription factors link mouse WAP-T mammary tumors with human breast cancer
AU - Otto, Benjamin
AU - Streichert, Thomas
AU - Wegwitz, Florian
AU - Gevensleben, Heidrun
AU - Klätschke, Kristin
AU - Wagener, Christoph
AU - Deppert, Wolfgang
AU - Tolstonog, Genrich V
N1 - Copyright © 2012 UICC.
PY - 2013/3/15
Y1 - 2013/3/15
N2 - Mouse models are important tools to decipher the molecular mechanisms of mammary carcinogenesis and to mimic the respective human disease. Despite sharing common phenotypic and genetic features, the proper translation of murine models to human breast cancer remains a challenging task. In a previous study we showed that in the SV40 transgenic WAP-T mice an active Met-pathway and epithelial-mesenchymal characteristics distinguish low- and high-grade mammary carcinoma. To assign these murine tumors to corresponding human tumors we here incorporated the analysis of expression of transcription factor (TF) coding genes and show that thereby a more accurate interspecies translation can be achieved. We describe a novel cross-species translation procedure and demonstrate that expression of unsupervised selected TFs, such as ELF5, HOXA5 and TFCP2L1, can clearly distinguish between the human molecular breast cancer subtypes--or as, for example, expression of TFAP2B between yet unclassified subgroups. By integrating different levels of information like histology, gene set enrichment, expression of differentiation markers and TFs we conclude that tumors in WAP-T mice exhibit similarities to both, human basal-like and non-basal-like subtypes. We furthermore suggest that the low- and high-grade WAP-T tumor phenotypes might arise from distinct cells of tumor origin. Our results underscore the importance of TFs as common cross-species denominators in the regulatory networks underlying mammary carcinogenesis.
AB - Mouse models are important tools to decipher the molecular mechanisms of mammary carcinogenesis and to mimic the respective human disease. Despite sharing common phenotypic and genetic features, the proper translation of murine models to human breast cancer remains a challenging task. In a previous study we showed that in the SV40 transgenic WAP-T mice an active Met-pathway and epithelial-mesenchymal characteristics distinguish low- and high-grade mammary carcinoma. To assign these murine tumors to corresponding human tumors we here incorporated the analysis of expression of transcription factor (TF) coding genes and show that thereby a more accurate interspecies translation can be achieved. We describe a novel cross-species translation procedure and demonstrate that expression of unsupervised selected TFs, such as ELF5, HOXA5 and TFCP2L1, can clearly distinguish between the human molecular breast cancer subtypes--or as, for example, expression of TFAP2B between yet unclassified subgroups. By integrating different levels of information like histology, gene set enrichment, expression of differentiation markers and TFs we conclude that tumors in WAP-T mice exhibit similarities to both, human basal-like and non-basal-like subtypes. We furthermore suggest that the low- and high-grade WAP-T tumor phenotypes might arise from distinct cells of tumor origin. Our results underscore the importance of TFs as common cross-species denominators in the regulatory networks underlying mammary carcinogenesis.
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred BALB C
KW - Phenotype
KW - Cell Line, Tumor
KW - Gene Expression Profiling
KW - Mice, Transgenic
KW - Breast Neoplasms/etiology/metabolism
KW - DNA-Binding Proteins/physiology
KW - Mammary Neoplasms, Experimental/etiology/metabolism
KW - Transcription Factors/physiology
KW - Animals
KW - Humans
KW - Female
KW - Mice
KW - Mice, Inbred BALB C
KW - Phenotype
KW - Cell Line, Tumor
KW - Gene Expression Profiling
KW - Mice, Transgenic
KW - Breast Neoplasms/etiology/metabolism
KW - DNA-Binding Proteins/physiology
KW - Mammary Neoplasms, Experimental/etiology/metabolism
KW - Transcription Factors/physiology
U2 - 10.1002/ijc.27941
DO - 10.1002/ijc.27941
M3 - SCORING: Journal article
C2 - 23161608
VL - 132
SP - 1311
EP - 1322
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 6
M1 - 6
ER -
