This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Desprez, P. Y.
Right arrow Articles by Campisi, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Desprez, P. Y.
Right arrow Articles by Campisi, J.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Jun 1995, 3398-3404, Vol 15, No. 6
Copyright © 1995, American Society for Microbiology

Suppression of mammary epithelial cell differentiation by the helix- loop-helix protein Id-1

PY Desprez, E Hara, MJ Bissell and J Campisi
Department of Cancer Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.

Cell proliferation and differentiation are precisely coordinated during the development and maturation of the mammary gland, and this balance invariably is disrupted during carcinogenesis. Little is known about the cell-specific transcription factors that regulate these processes in the mammary gland. The mouse mammary epithelial cell line SCp2 grows well under standard culture conditions but arrests growth, forms alveolus-like structures, and expresses beta-casein, a differentiation marker, 4 to 5 days after exposure to basement membrane and lactogenic hormones (differentiation signals). We show that this differentiation entails a marked decline in the expression of Id-1, a helix-loop-helix (HLH) protein that inactivates basic HLH transcription factors in other cell types. SCp2 cells stably transfected with an Id-1 expression vector grew more rapidly than control cells under standard conditions, but in response to differentiation signals, they arrested growth and formed three-dimensional structures similar to those of control cells. Id-1-expressing cells did not, however, express beta-casein. Moreover, 8 to 10 days after receiving differentiation signals, they lost three- dimensional organization, invaded the basement membrane, and then resumed growth. SCp2 cells expressing an Id-1 antisense vector grew more slowly than controls; in response to differentiation signals, they remained stably growth arrested and fully differentiated, as did control cells. We suggest that Id-1 renders cells refractory to differentiation signals and receptive to growth signals by inactivating one or more basic HLH proteins that coordinate growth and differentiation in the mammary epithelium.


This article has been cited by other articles:

  • Lew, B. J., Collins, L. L., O'Reilly, M. A., Lawrence, B. P. (2009). Activation of the Aryl Hydrocarbon Receptor during Different Critical Windows in Pregnancy Alters Mammary Epithelial Cell Proliferation and Differentiation. Toxicol Sci 111: 151-162 [Abstract] [Full Text]  
  • Caldon, C. E., Swarbrick, A., Lee, C. S.L., Sutherland, R. L., Musgrove, E. A. (2008). The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini. Cancer Res. 68: 3026-3036 [Abstract] [Full Text]  
  • Gautschi, O., Tepper, C. G., Purnell, P. R., Izumiya, Y., Evans, C. P., Green, T. P., Desprez, P. Y., Lara, P. N., Gandara, D. R., Mack, P. C., Kung, H.-J. (2008). Regulation of Id1 Expression by Src: Implications for Targeting of the Bone Morphogenetic Protein Pathway in Cancer. Cancer Res. 68: 2250-2258 [Abstract] [Full Text]  
  • Tang, B., Yoo, N., Vu, M., Mamura, M., Nam, J.-S., Ooshima, A., Du, Z., Desprez, P.-Y., Anver, M. R., Michalowska, A. M., Shih, J., Parks, W. T., Wakefield, L. M. (2007). Transforming Growth Factor-{beta} Can Suppress Tumorigenesis through Effects on the Putative Cancer Stem or Early Progenitor Cell and Committed Progeny in a Breast Cancer Xenograft Model. Cancer Res. 67: 8643-8652 [Abstract] [Full Text]  
  • Huh, J.-I., Qiu, T. H., Chandramouli, G. V. R., Charles, R., Wiench, M., Hager, G. L., Catena, R., Calvo, A., LaVallee, T. M., Desprez, P.-Y., Green, J. E. (2007). 2-Methoxyestradiol Induces Mammary Gland Differentiation through Amphiregulin-Epithelial Growth Factor Receptor-Mediated Signaling: Molecular Distinctions from the Mammary Gland of Pregnant Mice. Endocrinology 148: 1266-1277 [Abstract] [Full Text]  
  • Perk, J., Gil-Bazo, I., Chin, Y., de Candia, P., Chen, J. J.S., Zhao, Y., Chao, S., Cheong, W., Ke, Y., Al-Ahmadie, H., Gerald, W. L., Brogi, E., Benezra, R. (2006). Reassessment of Id1 Protein Expression in Human Mammary, Prostate, and Bladder Cancers Using a Monospecific Rabbit Monoclonal Anti-Id1 Antibody.. Cancer Res. 66: 10870-10877 [Abstract] [Full Text]  
  • Maitra, U., Seo, J., Lozano, M. M., Dudley, J. P. (2006). Differentiation-Induced Cleavage of Cutl1/CDP Generates a Novel Dominant-Negative Isoform That Regulates Mammary Gene Expression. Mol. Cell. Biol. 26: 7466-7478 [Abstract] [Full Text]  
  • Jankiewicz, M., Groner, B., Desrivieres, S. (2006). Mammalian Target of Rapamycin Regulates the Growth of Mammary Epithelial Cells through the Inhibitor of Deoxyribonucleic Acid Binding Id1 and Their Functional Differentiation through Id2. Mol. Endocrinol. 20: 2369-2381 [Abstract] [Full Text]  
  • Zhao, Y., Johansson, C., Tran, T., Bettencourt, R., Itahana, Y., Desprez, P.-Y., Konieczny, S. F. (2006). Identification of a Basic Helix-Loop-Helix Transcription Factor Expressed in Mammary Gland Alveolar Cells and Required for Maintenance of the Differentiated State. Mol. Endocrinol. 20: 2187-2198 [Abstract] [Full Text]  
  • Jones, J. M., Montcouquiol, M., Dabdoub, A., Woods, C., Kelley, M. W. (2006). Inhibitors of Differentiation and DNA Binding (Ids) Regulate Math1 and Hair Cell Formation during the Development of the Organ of Corti. J. Neurosci. 26: 550-558 [Abstract] [Full Text]  
  • Sumida, T., Itahana, Y., Hamakawa, H., Desprez, P.-Y. (2004). Reduction of Human Metastatic Breast Cancer Cell Aggressiveness on Introduction of Either Form A or B of the Progesterone Receptor and Then Treatment with Progestins. Cancer Res. 64: 7886-7892 [Abstract] [Full Text]  
  • Forrest, S., McNamara, C. (2004). Id Family of Transcription Factors and Vascular Lesion Formation. Arterioscler. Thromb. Vasc. Bio. 24: 2014-2020 [Abstract] [Full Text]  
  • Lofstedt, T., Jogi, A., Sigvardsson, M., Gradin, K., Poellinger, L., Pahlman, S., Axelson, H. (2004). Induction of ID2 Expression by Hypoxia-inducible Factor-1: A ROLE IN DEDIFFERENTIATION OF HYPOXIC NEUROBLASTOMA CELLS. J. Biol. Chem. 279: 39223-39231 [Abstract] [Full Text]  
  • Zhang, K.-X., Ward, K. R., Schrader, J. W. (2004). Multiple Aspects of the Phenotype of Mammary Epithelial Cells Transformed by Expression of Activated M-Ras Depend on an Autocrine Mechanism Mediated by Hepatocyte Growth Factor/Scatter Factor. Mol Cancer Res 2: 242-255 [Abstract] [Full Text]  
  • Ling, M.-T., Wang, X., Lee, D. T., Tam, P.C., Tsao, S.-W., Wong, Y.-C. (2004). Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R). Carcinogenesis 25: 517-525 [Abstract] [Full Text]  
  • Shan, L., Yu, M., Qiu, C., Snyderwine, E. G. (2003). Id4 Regulates Mammary Epithelial Cell Growth and Differentiation and Is Overexpressed in Rat Mammary Gland Carcinomas. Am. J. Pathol. 163: 2495-2502 [Abstract] [Full Text]  
  • Fong, S., Itahana, Y., Sumida, T., Singh, J., Coppe, J.-P., Liu, Y., Richards, P. C., Bennington, J. L., Lee, N. M., Debs, R. J., Desprez, P.-Y. (2003). Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis. Proc. Natl. Acad. Sci. USA 100: 13543-13548 [Abstract] [Full Text]  
  • Itahana, Y., Singh, J., Sumida, T., Coppe, J.-P., Parrinello, S., Bennington, J. L., Desprez, P.-Y. (2003). Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells. Cancer Res. 63: 7098-7105 [Abstract] [Full Text]  
  • Alway, S. E., Degens, H., Krishnamurthy, G., Chaudhrai, A. (2003). Denervation Stimulates Apoptosis But Not Id2 Expression in Hindlimb Muscles of Aged Rats. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58: B687-697 [Abstract] [Full Text]  
  • Navarro, M., Valentinis, B., Belletti, B., Romano, G., Reiss, K., Baserga, R. (2001). Regulation of Id2 Gene Expression by the Type 1 IGF Receptor and the Insulin Receptor Substrate-1. Endocrinology 142: 5149-5157 [Abstract] [Full Text]  
  • Parrinello, S., Lin, C. Q., Murata, K., Itahana, Y., Singh, J., Krtolica, A., Campisi, J., Desprez, P.-Y. (2001). Id-1, ITF-2, and Id-2 Comprise a Network of Helix-Loop-Helix Proteins That Regulate Mammary Epithelial Cell Proliferation, Differentiation, and Apoptosis. J. Biol. Chem. 276: 39213-39219 [Abstract] [Full Text]  
  • Prisco, M., Peruzzi, F., Belletti, B., Baserga, R. (2001). Regulation of Id Gene Expression by Type I Insulin-Like Growth Factor: Roles of STAT3 and the Tyrosine 950 Residue of the Receptor. Mol. Cell. Biol. 21: 5447-5458 [Abstract] [Full Text]  
  • Hu, Y. C., Lam, K. Y., Law, S., Wong, J., Srivastava, G. (2001). Identification of Differentially Expressed Genes in Esophageal Squamous Cell Carcinoma (ESCC) by cDNA Expression Array: Overexpression of Fra-1, Neogenin, Id-1, and CDC25B Genes in ESCC. Clin. Cancer Res. 7: 2213-2221 [Abstract] [Full Text]  
  • Ouyang, X.S., Wang, X., Lee, D.T.W., Tsao, S.W., Wong, Y.C. (2001). Up-regulation of TRPM-2, MMP-7 and ID-1 during sex hormone-induced prostate carcinogenesis in the Noble rat. Carcinogenesis 22: 965-973 [Abstract] [Full Text]  
  • Beger, C., Pierce, L. N., Kruger, M., Marcusson, E. G., Robbins, J. M., Welcsh, P., Welch, P. J., Welte, K., King, M.-C., Barber, J. R., Wong-Staal, F. (2001). Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach. Proc. Natl. Acad. Sci. USA 98: 130-135 [Abstract] [Full Text]  
  • Adell, T., Gómez-Cuadrado, A., Skoudy, A., Pettengill, O. S., Longnecker, D. S., Real, F. X. (2000). Role of the Basic Helix-Loop-Helix Transcription Factor p48 in the Differentiation Phenotype of Exocrine Pancreas Cancer Cells. Cell Growth Differ. 11: 137-147 [Abstract] [Full Text]  
  • Barcellos-Hoff, M. H., Ravani, S. A. (2000). Irradiated Mammary Gland Stroma Promotes the Expression of Tumorigenic Potential by Unirradiated Epithelial Cells. Cancer Res. 60: 1254-1260 [Abstract] [Full Text]  
  • Lin, C. Q., Singh, J., Murata, K., Itahana, Y., Parrinello, S., Liang, S. H., Gillett, C. E., Campisi, J., Desprez, P.-Y. (2000). A Role for Id-1 in the Aggressive Phenotype and Steroid Hormone Response of Human Breast Cancer Cells. Cancer Res. 60: 1332-1340 [Abstract] [Full Text]  
  • Norton, J. (2000). ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J. Cell Sci. 113: 3897-3905 [Abstract]  
  • Pujuguet, P, Simian, M, Liaw, J, Timpl, R, Werb, Z, Bissell, M. (2000). Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression. J. Cell Sci. 113: 849-858 [Abstract]  
  • Pan, L., Sato, S., Frederick, J. P., Sun, X.-H., Zhuang, Y. (1999). Impaired Immune Responses and B-Cell Proliferation in Mice Lacking the Id3 Gene. Mol. Cell. Biol. 19: 5969-5980 [Abstract] [Full Text]  
  • Maruyama, H., Kleeff, J., Wildi, S., Friess, H., Buchler, M. W., Israel, M. A., Korc, M. (1999). Id-1 and Id-2 Are Overexpressed in Pancreatic Cancer and in Dysplastic Lesions in Chronic Pancreatitis. Am. J. Pathol. 155: 815-822 [Abstract] [Full Text]  
  • Outinen, P. A., Sood, S. K., Pfeifer, S. I., Pamidi, S., Podor, T. J., Li, J., Weitz, J. I., Austin, R. C. (1999). Homocysteine-Induced Endoplasmic Reticulum Stress and Growth Arrest Leads to Specific Changes in Gene Expression in Human Vascular Endothelial Cells. Blood 94: 959-967 [Abstract] [Full Text]  
  • Markus, M., Benezra, R. (1999). Two Isoforms of Protein Disulfide Isomerase Alter the Dimerization Status of E2A Proteins by a Redox Mechanism. J. Biol. Chem. 274: 1040-1049 [Abstract] [Full Text]  
  • Katsube, T., Takahisa, M., Ueda, R., Hashimoto, N., Kobayashi, M., Togashi, S. (1998). Cortactin Associates with the Cell-Cell Junction Protein ZO-1 in both Drosophila and Mouse. J. Biol. Chem. 273: 29672-29677 [Abstract] [Full Text]  
  • Wice, B. M., Gordon, J. I. (1998). Forced Expression of Id-1 in the Adult Mouse Small Intestinal Epithelium Is Associated with Development of Adenomas. J. Biol. Chem. 273: 25310-25319 [Abstract] [Full Text]  
  • Florio, M., Hernandez, M.-C., Yang, H., Shu, H.-K., Cleveland, J. L., Israel, M. A. (1998). Id2 Promotes Apoptosis by a Novel Mechanism Independent of Dimerization to Basic Helix-Loop-Helix Factors. Mol. Cell. Biol. 18: 5435-5444 [Abstract] [Full Text]  
  • Desprez, P.-Y., Lin, C. Q., Thomasset, N., Sympson, C. J., Bissell, M. J., Campisi, J. (1998). A Novel Pathway for Mammary Epithelial Cell Invasion Induced by the Helix-Loop-Helix Protein Id-1. Mol. Cell. Biol. 18: 4577-4588 [Abstract] [Full Text]  
  • Norton, J. D., Atherton, G. T. (1998). Coupling of Cell Growth Control and Apoptosis Functions of Id Proteins. Mol. Cell. Biol. 18: 2371-2381 [Abstract] [Full Text]  
  • Pagliuca, A., Cannada-Bartoli, P., Lania, L. (1998). A Role for Sp and Helix-Loop-Helix Transcription Factors in the Regulation of the Human Id4 Gene Promoter Activity. J. Biol. Chem. 273: 7668-7674 [Abstract] [Full Text]  
  • Weaver, V.M., Petersen, O.W., Wang, F., Larabell, C.A., Briand, P., Damsky, C., Bissell, M.J. (1997). Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies. JCB 137: 231-245 [Abstract] [Full Text]  
  • Prowse, D. M., Bolgan, L., Molnar, A., Dotto, G. P. (1997). Involvement of the Sp3 Transcription Factor in Induction of p21Cip1/WAF1 in Keratinocyte Differentiation. J. Biol. Chem. 272: 1308-1314 [Abstract] [Full Text]  
  • Singh, J., Itahana, Y., Parrinello, S., Murata, K., Desprez, P.-Y. (2001). Molecular Cloning and Characterization of a Zinc Finger Protein Involved in Id-1-stimulated Mammary Epithelial Cell Growth. J. Biol. Chem. 276: 11852-11858 [Abstract] [Full Text]  
  • Belletti, B., Prisco, M., Morrione, A., Valentinis, B., Navarro, M., Baserga, R. (2001). Regulation of Id2 Gene Expression by the Insulin-like Growth Factor I Receptor Requires Signaling by Phosphatidylinositol 3-Kinase. J. Biol. Chem. 276: 13867-13874 [Abstract] [Full Text]  
  • Woo, P. L., Cercek, A., Desprez, P.-Y., Firestone, G. L. (2000). Involvement of the Helix-Loop-Helix Protein Id-1 in the Glucocorticoid Regulation of Tight Junctions in Mammary Epithelial Cells. J. Biol. Chem. 275: 28649-28658 [Abstract] [Full Text]  
  • Ikawa, T., Fujimoto, S., Kawamoto, H., Katsura, Y., Yokota, Y. (2001). Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc. Natl. Acad. Sci. USA 98: 5164-5169 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»