ABSTRACT
Cell lines 4A4 and 2C5 are the respective metastatic and non-metastatic variants of the human mammary carcinoma cell line MDA-MB-435 in the nude mouse system. We compared the transcriptional profile of approximately 5000 full-length genies using the Affymetrix HuGene FL Array technology. We have shown that the metastatic phenotype is mediated by different functional categories of genes, e.g. genes involved in immune response, genes responsible for tumor antigens, genes involved in migration and invasion, genes involved in mediating signal transduction, genes responsible for transcription factors, genes involved in phospholipid signaling, genes involved in modulation of extracellular matrix and cytoskeleton, genes with a cell-type specific mode of expression and genes which do not fit into the subclasses as defined above. Our results suggest an important role of Autocrine Motility Factor (AMF) as a mediator of metastasis in this system.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Neoplasm Metastasis , Transcription, Genetic , Animals , Blotting, Northern , Cell Line , Down-Regulation , Female , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Oligonucleotide Array Sequence Analysis , Phenotype , RNA, Messenger/metabolism , Signal Transduction , Tumor Cells, Cultured , Up-RegulationABSTRACT
In order to identify genes associated with metastasis of mammary carcinoma, we compared the transcriptional profile (Affymetrix chip technology) of two cell lines derived from primary mammary carcinoma, three cell lines derived from bone marrow micrometastasis, a cell line derived from a lymph node metastasis as well as a cell line derived from malignant ascites. We found that 11 genes (0.16%) were up-regulated in all five cell lines derived from metastasis and 32 genes (0.45%) were up-regulated in four of these cell lines. Sixteen genes (0.23%) were down-regulated in the five metastatic cell lines, while 24 genes (0.34%) were down-regulated in four of the metastatic cell lines. The usefulness of our system for the identification of genes associated with metastasis of mammary carcinoma is demonstrated by the identification of genes which have already been implicated in metastasis of mammary carcinoma. This suggests that further evaluation of identified de-regulated genes, which until now have not been seen in context with metastasis of mammary carcinoma, should be undertaken.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Oligonucleotide Array Sequence Analysis/methods , Bone Marrow Neoplasms/genetics , Bone Marrow Neoplasms/secondary , Breast Neoplasms/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Neoplasm Metastasis , Transcription, Genetic , Tumor Cells, Cultured , Up-RegulationABSTRACT
In order to identify genes associated with metastasis of ductal pancreatic adenocarcinoma we investigated pancreatic tumor cell lines derived from an orthotopic pancreatic tumor model in SCID mice. Transcriptional profiling (Affymetrix Gene Chip Technology) was performed with cell lines derived from the primary tumor and metastatic lesions such as mesentery, liver and lungs. We scored for genes commonly deregulated in the cell lines derived from the metastatic lesions. Of 7070 genes investigated, 59 (0.83%) were found to be deregulated in the cell lines derived from the metastatic lesions. We grouped these genes into different categories such as transcription, translation, cytoskeleton, cell adhesion, chromosome instability, tumor suppressor genes, enzymes and "others". The most remarkable features of the system are the up-regulation of high mobility group protein HMG-I (Y), twenty-one ribosomal proteins, GAPDH and the laminin receptor in the cell lines derived from the metastatic lesions, whereas tumor suppressor genes such as maspin and RB1 were down-regulated. Inhibition or reconstitution of the activity of these targets are an emerging strategy for inhibition of metastasis in this system.
