HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takaoka, A. S. Articles by Hirohashi, S. Search for Related Content PubMed PubMed Citation Articles by Takaoka, A. S. Articles by Hirohashi, S. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 50, 33848-33855, December 11, 1998

Cloning and Characterization of the Human ₄-Integrin Gene Promoter and Enhancers

Asako Suzuki Takaoka^§, Tesshi Yamada, Masahiro Gotoh, Yae Kanai, Kohzoh Imai^§, and Setsuo Hirohashi

From the  Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 and the ^§ First Department of Internal Medicine, Sapporo Medical University School of Medicine, Minami-1, Nishi-16, Chuo-ku, Sapporo 060-8543, Japan

The cell-surface adhesion molecule ₆₄-integrin is a receptor for laminins and a component of hemidesmosomes. ₄-Integrin expression is restricted to proliferating basal keratinocytes in the epidermis and is suppressed when differentiation commences. Altered ₄-integrin expression levels correlate significantly with the aggressive behavior of cancers. In order to clarify the mechanisms that regulate transcription of the ₄-integrin gene, we cloned its 5'-flanking region. This 5'-flanking region was found to have a high G + C content and not to contain either TATA or CAAT boxes. Nested delimitation and reporter analyses mapped a basal promoter to nucleotides 106 to +105, surrounding the most proximal transcription initiation site. Gel retardation and mutational analyses revealed that cooperation between AP1 and Ets, interacting with other factors, mediated the promoter activity. In addition to the promoter element, enhancer activity was found in the first intron (+1905/+3933) and in a sequence upstream of the promoter region (414/107). These findings should facilitate our understanding of the regulation of ₄-integrin gene expression in processes such as cell growth and differentiation, apoptosis, and cancer development and metastasis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				F. E. Turner, S. Broad, F. L. Khanim, A. Jeanes, S. Talma, S. Hughes, C. Tselepis, and N. A. Hotchin Slug Regulates Integrin Expression and Cell Proliferation in Human Epidermal Keratinocytes J. Biol. Chem., July 28, 2006; 281(30): 21321 - 21331. [Abstract] [Full Text] [PDF]

				S.-O. Yoon, S. Shin, and A. M. Mercurio Ras Stimulation of E2F Activity and a Consequent E2F Regulation of Integrin {alpha}6{beta}4 Promote the Invasion of Breast Carcinoma Cells. Cancer Res., June 15, 2006; 66(12): 6288 - 6295. [Abstract] [Full Text] [PDF]

				A. Bertotti, P. M. Comoglio, and L. Trusolino {beta}4 Integrin Is a Transforming Molecule that Unleashes Met Tyrosine Kinase Tumorigenesis Cancer Res., December 1, 2005; 65(23): 10674 - 10679. [Abstract] [Full Text] [PDF]

				M. Oldak, H. Smola, M. Aumailley, F. Rivero, H. Pfister, and S. Smola-Hess The Human Papillomavirus Type 8 E2 Protein Suppresses {beta}4-Integrin Expression in Primary Human Keratinocytes J. Virol., October 1, 2004; 78(19): 10738 - 10746. [Abstract] [Full Text] [PDF]

				D. Kita, T. Takino, M. Nakada, T. Takahashi, J. Yamashita, and H. Sato Expression of Dominant-negative Form of Ets-1 Suppresses Fibronectin-stimulated Cell Adhesion and Migration Through Down-Regulation of Integrin {alpha}5 Expression in U251 Glioma Cell Line Cancer Res., November 1, 2001; 61(21): 7985 - 7991. [Abstract] [Full Text] [PDF]

				S. Sinha, L. Degenstein, C. Copenhaver, and E. Fuchs Defining the Regulatory Factors Required for Epidermal Gene Expression Mol. Cell. Biol., April 1, 2000; 20(7): 2543 - 2555. [Abstract] [Full Text]