Distinctive gene expression patterns in human mammary epithelial cells and breast cancers.

cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors. Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples. By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster, the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined. Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples. Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectively. Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis. These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors.

[1]  E. Robecchi.  [Pathology of the breast]. , 1954, Minerva ginecologica.

[2]  L. Hayflick.  THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. , 1965, Experimental cell research.

[3]  E. L. Springer,et al.  Two syngeneic cell lines from human breast tissue: the aneuploid mammary epithelial (Hs578T) and the diploid myoepithelial (Hs578Bst) cell lines. , 1977, Journal of the National Cancer Institute.

[4]  M. Abercrombie,et al.  Contact inhibition and malignancy , 1979, Nature.

[5]  K. Hagino-Yamagishi,et al.  [Oncogene]. , 2019, Gan to kagaku ryoho. Cancer & chemotherapy.

[6]  S. Goldstein,et al.  High-voltage electron microscopy of human diploid fibroblasts during ageing in vitro. Morphometric analysis of mitochondria. , 1984, Experimental cell research.

[7]  J. Chebath,et al.  Structure of two forms of the interferon‐induced (2′‐5′) oligo A synthetase of human cells based on cDNAs and gene sequences. , 1985, The EMBO journal.

[8]  R. Warnke,et al.  Advantages of detecting monoclonal antibody binding to tissue sections with biotin and avidin reagents in Coplin jars. , 1986, American journal of clinical pathology.

[9]  B. Korant,et al.  Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence. , 1986, The Journal of biological chemistry.

[10]  I. Stamenkovic,et al.  Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein , 1988, The Journal of experimental medicine.

[11]  J. Gerdes.  Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. , 1990, Seminars in cancer biology.

[12]  B. Casto,et al.  Transformation of human epithelial cells : molecular and oncogenetic mechanisms , 1992 .

[13]  J. Gerdes,et al.  The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins , 1993, The Journal of cell biology.

[14]  M. Gerretsen,et al.  A phase III randomised trial of cisplatinum, methotrextate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. Liverpool Head and Neck Oncology Group. , 1990, British Journal of Cancer.

[15]  P. Yaswen,et al.  TGFβ induction of extracellular matrix associated proteins in normal and transformed human mammary epithelial cells in culture is independent of growth effects , 1993 .

[16]  P. Yaswen,et al.  Blockage of EGF receptor signal transduction causes reversible arrest of normal and immortal human mammary epithelial cells with synchronous reentry into the cell cycle. , 1993, Experimental cell research.

[17]  J. Taylor‐Papadimitriou,et al.  Branching morphogenesis of human mammary epithelial cells in collagen gels. , 1994, Journal of cell science.

[18]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[19]  L. Weber,et al.  Accelerated growth and senescence of arterial endothelial cells expressing the small molecular weight heat‐shock protein HSP27 , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  C. Watson,et al.  Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts. , 1995, British Journal of Cancer.

[21]  L. Penland,et al.  Use of a cDNA microarray to analyse gene expression patterns in human cancer , 1996, Nature Genetics.

[22]  P. Brown,et al.  A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. , 1996, Genome research.

[23]  M J Bissell,et al.  Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. , 1996, Physiological reviews.

[24]  Galloway Da,et al.  HUMAN PAPILLOMAVIRUS TYPE 16 E7 ALLEVIATES A PROLIFERATION BLOCK IN EARLY PASSAGE HUMAN MAMMARY EPITHELIAL CELLS , 1996 .

[25]  A. Jetten,et al.  Gamma-interferon induces an irreversible growth arrest in mid-G1 in mammary epithelial cells which correlates with a block in hyperphosphorylation of retinoblastoma. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[26]  P. Brown,et al.  Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  J. Darnell,et al.  Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  I. Julkunen,et al.  Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages. , 1997, Journal of immunology.

[29]  J. Darnell.  STATs and gene regulation. , 1997, Science.

[30]  P. Yaswen,et al.  Gradual phenotypic conversion associated with immortalization of cultured human mammary epithelial cells. , 1997, Molecular biology of the cell.

[31]  V. Jordan,et al.  MCF-7: the first hormone-responsive breast cancer cell line. , 1997, Cancer research.

[32]  R. Snell,et al.  Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[34]  L. Hennighausen,et al.  Stat5a is mandatory for adult mammary gland development and lactogenesis. , 1997, Genes & development.

[35]  M. Crompton,et al.  Expression of v-src in mammary epithelial cells induces transcription via STAT3. , 1998, The Biochemical journal.

[36]  M. Bittner,et al.  Data management and analysis for gene expression arrays , 1998, Nature Genetics.

[37]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[38]  R. Jove,et al.  Activation of STAT transcription factors in oncogenic tyrosine kinase signaling. , 1998, Journal of biomedical science.

[39]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  D. Botstein,et al.  The transcriptional program in the response of human fibroblasts to serum. , 1999, Science.

[41]  D. Botstein,et al.  Exploring the new world of the genome with DNA microarrays , 1999, Nature Genetics.