Abstract
Several lines of evidence suggest that chromosome 8 is likely to harbor tumor suppressor gene(s) involved in breast cancer. We have shown previously that microcell-mediated transfer of human chromosome 8 into the breast cancer cell line MDA-MB-231 results in reversion of tumorigenicity of these cells and is accompanied by expression changes of a clinically relevant set of genes. In the present study we demonstrate that the transfer of human chromosome 8 into another breast cancer cell line, CAL51, results in hybrids characterized by suppression of tumorigenicity in vitro and in vivo as compared with the parental cells. Loss of the transferred chromosome 8 results in reappearance of the CAL51 phenotype. Oligonucleotide microarray analysis identified 78 probe sets differentially expressed in the hybrids as compared with CAL51 and the rerevertant cells. The majority of these genes is involved in signal transduction, developmental processes, angiogenesis, cadherin signaling, Wnt signaling or inflammation. It is of particular interest that the 78-gene signature is also reflected in a panel of breast tumors, lymph node and distant metastases, and is correlated with several prognostic markers including tumor size, grading, metastatic behavior and estrogen receptor status. As opposed to the corresponding non-tumorigenic phenotypes demonstrated for the MDA-MB-231-derived and CAL51-derived microcell hybrids, the respective differentially expressed genes strongly differ from each other. However, it was of special interest that the majority of genes of both gene sets could be integrated into a similar spectrum of biological processes and pathways. Our findings provide an experimental system to identify and evaluate genes but, more importantly, signatures of biological processes and pathways involved in the development and/or progression of breast cancer.
Highlights
We have shown that overexpression of TGF-β1 in mammary epithelial cells suppresses the development of carcinomas and that expression of a dominant negative type II TGF-β receptor (DNIIR) in mammary epithelial cells under control of the MMTV promoter/enhancer increases the incidence of erbB2 in carcinomas accompanied by Tgfbr2fspKO fibroblasts
We found that the frequency of the IVS10-6T>G is characterized by multiple physiologic abnormalities, including mutation was not increased in breast cancer cases as compared with neurodegeneration, immunologic abnormalities, cancer predisposition, controls
We examined the incidence of tumors the hypothesis that Single nucleotide polymorphisms (SNPs) in the regulatory regions of genes that create formed in these ERα knockout mice bearing the Wnt-1 transgene
Summary
Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity. Several human genetic diseases are known to be or suspected to be due to defects in DNA repair or cell cycle control Some of these patients are radiation sensitive and/or predisposed for cancer as a cause of mutations in genes involved in these cellular pathways. Microarray-based comparative genomic hybridization (arrayCGH) allows the construction of high-resolution genome-wide maps of copy number alterations, and statistical software packages are available for exploring and analysing array-CGH data (see, for example, [2,3]), facilitating the delineation of the boundaries of CNAs in individual tumors and thereby localizing and identifying potential oncogenes and tumor suppressor genes. The aim of this study was to evaluate the prognostic value of gene expression-based classification as well as established prognostic markers, including mutation status of the TP53 gene, in a group of breast cancer patients with long-term (>10 years) fol The aim of this study was to compare MR spectroscopic findings from breast cancer tissue with histological grading of tumor and patient lymph node status
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
