Abstract
Pathogenesis of cancer begins as hyperplastic lesions; some lesions remain benign, while others progress to malignancy. An increase in cell proliferation rates and changes in tissue architecture are two properties commonly observed in hyperplastic lesions. A great deal is known about the molecular events that regulate cell proliferation and the knowledge gained is widely used for development of diagnostic and treatment tools. Our understanding of the mechanisms that deregulate tissue architecture is poor, and hence it is understandable that the use of architectural features to determine prognosis of early lesions has varying success. We used polarized epithelial cells and an inducible method of ErbB2 activation to investigate whether the cell architecture influences ErbB2-induced gene expression and to investigate how activation of ErbB2 disrupts epithelial cell architecture. Activation of ErbB2 in three-dimensional epithelial acini-like structures leads to expression of a unique set of genes that was not observed when ErbB2 was activated in cells grown on plastic dishes, suggesting that the cell architecture can have significant influence on ErbB2-induced gene expression. To investigate the effect of ErbB2 activation on epithelial architecture, we activated ErbB2 in polarized epithelial cells. ErbB2 induced a loss in apical–basal polarity, re-initiated proliferation and induced multilayering of epithelial sheets. These changes correlate with the ability of ErbB2 to regulate the Par complex, a protein complex known to regulate establishment of epithelial cell polarity. Inactivation of atypical protein kinase C, a component of the Par complex, cooperates with ErbB2 to disrupt polarized epithelial cells, suggesting that the Par complex is a mediator of ErbB2-induced effects on polarized epithelial cells. In addition, we identify tricellular junctions, and not bicellular junctions, as a novel site for ErbB2 action in cultured epithelial cells and in primary breast cancer. We are thus beginning to gain novel insights into the molecular mechanisms that regulate early lesions.
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 Sign-in/Register to access full text options 
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.
