Expression profiling of epithelial plasticity in tumor progression.
Epithelial-to-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is increasingly considered as an important event during malignant tumor progression and metastasis. To identify molecular players involved in EMT and metastasis, we performed expression profiling of a set of combined in vitro/in vivo cellular models, based on clonal, fully polarized mammary epithelial cells. Seven closely related cell pairs were used, which were modified by defined oncogenes and/or external factors and showed specific aspects of epithelial plasticity relevant to cell migration, local invasion and metastasis. Since mRNA levels do not necessarily reflect protein levels in cells, we used an improved expression profiling method based on polysome-bound RNA, suitable to analyse global gene expression on Affymetrix chips. A substantial fraction of all regulated genes was found to be exclusively controlled at the translational level. Furthermore, profiling of the above multiple cell pairs allowed one to identify small numbers of genes by cluster analysis, specifically correlating gene expression with EMT, metastasis, scattering and/or oncogene function. A small set of genes specifically regulated during EMT was identified, including key regulators and signaling pathways involved in cell proliferation, epithelial polarity, survival and trans-differentiation to mesenchymal-like cells with invasive behavior.
Jechlinger
Martin
M
IMP, Research Institute for Molecular Pathology, Dr Bohrgasse 7, Vienna A-1030, Austria.
Grunert
Stefan
S
Tamir
Ido H
IH
Janda
Elzbieta
E
Lüdemann
Susanna
S
Waerner
Thomas
T
Seither
Peter
P
Weith
Andreas
A
Beug
Hartmut
H
Kraut
Norbert
N
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000473:pathology; D008648:Mesoderm / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009361:Neoplasm Invasiveness; D011132:Polyribosomes / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger