PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer.

The function of estrogen in breast cancer proliferation and progression is likely to be due to the expression of a repertoire of genes regulated by estrogen receptor (ER). Using suppression subtractive hybridization, we have isolated a set of 14 estrogen-responsive genes that was differentially expressed in MCF7 cells stimulated by beta-estradiol as compared with unstimulated cells. Tamoxifen repressed the expression of all 14 estrogen-responsive genes. Thirteen of the genes were induced within 6 h of estrogen treatment, indicating that these were early response genes in the ER-regulated pathway. PDZK1 and a new gene, GREB1, demonstrated a significant correlation with ER phenotype in a panel of breast cancer cell lines. Treatment with cycloheximide indicated that ER directly controls GREB1 expression. Three cDNAs (GREB1a, GREB1b, and GREB1c) were isolated by screening a MCF7 cDNA library. These three cDNAs of GREB1 shared extensive sequences through the open reading frame but had divergent 5' untranslated regions, indicating the possibility of multiple promoters regulated by beta-estradiol. Studies in primary breast cancers showed that PDZK1 and GREB1 were overexpressed in ER-positive breast cancers as compared with ER-negative breast cancers by 19-fold and 3.5-fold, respectively. GREB1 was also induced by beta-estradiol in the ER-positive endometrial cell line ECC-1. The pattern of expression suggests a critical role for these two genes in the response of tissues and tumors to beta-estradiol.

[1]  Y. Jan,et al.  Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases , 1995, Nature.

[2]  V. Jordan.  A current view of tamoxifen for the treatment and prevention of breast cancer , 1993 .

[3]  Rainer Fuchs,et al.  CLUSTAL V: improved software for multiple sequence alignment , 1992, Comput. Appl. Biosci..

[4]  W. D. Benton,et al.  Screening lambdagt recombinant clones by hybridization to single plaques in situ. , 1977, Science.

[5]  R. Coombes,et al.  Prediction of response to endocrine therapy in breast cancer using immunocytochemical assays for pS2, oestrogen receptor and progesterone receptor , 1993, International journal of cancer.

[6]  P. Chambon,et al.  Gastric Mucosa Abnormalities and Tumorigenesis in Mice Lacking the pS2 Trefoil Protein , 1996, Science.

[7]  P. Xu,et al.  Genetic, physical, and transcript map of the fld region on mouse chromosome 12. , 1999, Genomics.

[8]  H. Rochefort.  Oestrogens, proteases and breast cancer. From cell lines to clinical applications. , 1994, European journal of cancer.

[9]  H. Rochefort,et al.  Processing and estrogen regulation of the 52-kilodalton protein inside MCF7 breast cancer cells. , 1986, Endocrinology.

[10]  P. Chambon,et al.  Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. , 1982, Nucleic acids research.

[11]  M. Madsen,et al.  Resistance of human breast‐cancer cells to the pure steroidal anti‐estrogen ICI 182,780 is not associated with a general loss of estrogen‐receptor expression or lack of estrogen responsiveness , 1997, International journal of cancer.

[12]  M. Itoh,et al.  Afadin: A Novel Actin Filament–binding Protein with One PDZ Domain Localized at Cadherin-based Cell-to-Cell Adherens Junction , 1997, The Journal of cell biology.

[13]  B. Katzenellenbogen,et al.  Estrogen Receptor Regulation of the Na+/H+ Exchanger Regulatory Factor. , 1999, Endocrinology.

[14]  K. Mizuno,et al.  Cytoplasmic localization of LIM-kinase 1 is directed by a short sequence within the PDZ domain. , 1998, Experimental cell research.

[15]  C. Marck,et al.  'DNA Strider': a 'C' program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers. , 1988, Nucleic acids research.

[16]  E. Laws,et al.  Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. , 1998, The Journal of clinical endocrinology and metabolism.

[17]  N. Comella,et al.  Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[18]  P. Brown,et al.  Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes. , 1999, Nucleic acids research.

[19]  J. Prud'homme,et al.  Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours , 1993, Histopathology.

[20]  M. Pike,et al.  Hormonal chemoprevention of cancer in women , 1993, Science.

[21]  F. May,et al.  Identification and characterization of estrogen-regulated RNAs in human breast cancer cells. , 1988, The Journal of biological chemistry.

[22]  H. Rochefort,et al.  Effect of Estradiol on Nonmalignant Human Mammary Cells in Primary Culture a , 1984, Cancer research.

[23]  W. Miller,et al.  Thrombospondin in malignant and non-malignant breast tissue. , 1989, European journal of cancer & clinical oncology.

[24]  M. Lippman,et al.  The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. , 1976, Cancer research.

[25]  D. Chalbos,et al.  Estrogens stimulate cell proliferation and induce secretory proteins in a human breast cancer cell line (T47D). , 1982, The Journal of clinical endocrinology and metabolism.

[26]  F. May,et al.  Estrogen regulated messenger RNAs in human breast cancer cells. , 1995, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[27]  J. L. Donaher,et al.  Functional activity of ectopically expressed estrogen receptor is not sufficient for estrogen-mediated cyclin D1 expression. , 1999, Cancer research.

[28]  Peter J. Bryant,et al.  The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions , 1991, Cell.

[29]  R. Weigel,et al.  Moesin expression is associated with the estrogen receptor-negative breast cancer phenotype. , 1998, Surgery.

[30]  V. Jordan,et al.  Hormone receptor assays: clinical usefulness in the management of carcinoma of the breast. , 1988, Critical reviews in clinical laboratory sciences.

[31]  M. Kennedy,et al.  The rat brain postsynaptic density fraction contains a homolog of the drosophila discs-large tumor suppressor protein , 1992, Neuron.

[32]  H. Rochefort,et al.  Effect of estradiol on the ultrastructure of the MCF7 human breast cancer cells in culture. , 1982, Cancer research.

[33]  H. Rochefort.  Oestrogen- and anti-oestrogen-regulated genes in human breast cancer. , 1995, Ciba Foundation symposium.

[34]  Aaron P. Campbell,et al.  Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. McGuire,et al.  The value of estrogen and progesterone receptors in the treatment of breast cancer , 1980, Cancer.

[36]  T. Macalma,et al.  Purification and Characterization of an α-Actinin-binding PDZ-LIM Protein That Is Up-regulated during Muscle Differentiation* , 1999, The Journal of Biological Chemistry.

[37]  R. Elton,et al.  pS2 is an independent factor of good prognosis in primary breast cancer. , 1993, British Journal of Cancer.

[38]  E. J. Gregory,et al.  Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. , 1977, Cancer research.

[39]  P. Poyet,et al.  Control of the expression of thrombospondin 1 in human breast cancer cell lines. , 1994, Anticancer research.

[40]  P Chambon,et al.  Two distinct estrogen‐regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. , 1990, The EMBO journal.

[41]  D. Edwards,et al.  Estrogen regulation of specific messinger RNA's in human breast cancer cells. , 1980, Biochemical and biophysical research communications.

[42]  E. Holler,et al.  Effect of growth factors on estrogen receptor mediated gene expression , 1996, The Journal of Steroid Biochemistry and Molecular Biology.

[43]  B. Asselain,et al.  Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers. , 1996, British Journal of Cancer.

[44]  J. Knoll,et al.  PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein. , 1999, Laboratory investigation; a journal of technical methods and pathology.

[45]  R. Weigel,et al.  Differential screening and suppression subtractive hybridization identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line. , 1998, Nucleic acids research.

[46]  M. Granick,et al.  Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer. , 1996, The Journal of surgical research.

[47]  C. V. Van Itallie,et al.  The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. , 1993, Proceedings of the National Academy of Sciences of the United States of America.