QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 11 October 2005
doi: 10.1242/jcs.02616

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.02616v1 118/21/5005    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS 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 Dietze, E. C. Articles by Seewaldt, V. L. Search for Related Content PubMed PubMed Citation Articles by Dietze, E. C. Articles by Seewaldt, V. L. Social Bookmarking                         What's this?

CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5

¹ Division of Medical Oncology, Duke University, Durham, NC 27710, USA
² Division of Hematology and Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
³ Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
⁴ RIKEN, Tsukuba Institute, Ibaraki 305-0074, Japan
⁵ Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA

^* Author for correspondence (e-mail: seewa001{at}mc.duke.edu)

Accepted 3 August 2005

Interactions between normal mammary epithelial cells and extracellular matrix (ECM) are important for mammary gland homeostasis. Loss of interactions between ECM and normal mammary epithelial cells are thought to be an early event in mammary carcinogenesis. CREB-binding protein (CBP) is an important regulator of proliferation and apoptosis but the role of CBP in ECM signaling is poorly characterized. CBP was suppressed in basal-cytokeratin-positive HMECs (CK5/6⁺, CK14⁺, CK8^–, CK18^–, CK19^–). Suppression of CBP resulted in loss of reconstituted ECM-mediated growth control and apoptosis and loss of laminin-5 3-chain expression. Suppression of CBP in normal human mammary epithelial cells (HMECs) resulted in loss of CBP occupancy of the LAMA3A promoter and decreased LAMA3A promoter activity and laminin-5 -3 chain expression. Exogenous expression of CBP in CBP-negative HMECs that have lost reconstituted ECM-mediated growth regulation and apoptosis resulted in (1) CBP occupancy of the LAMA3A promoter, (2) increased LAMA3A activity and laminin-5 3-chain expression, and (3) enhancement of reconstituted ECM-mediated growth regulation and apoptosis. Similarly, suppression of laminin-5 3-chain expression in HMECs resulted in loss of reconstituted ECM-mediated growth control and apoptosis. These observations suggest that loss of CBP in basal-cytokeratin-positive HMECs results in loss of reconstituted ECM-mediated growth control and apoptosis through loss of LAMA3A activity and laminin-5 3-chain expression. Results in these studies may provide insight into early events in basal-type mammary carcinogenesis.

Key words: CBP, Basal cytokeratins, Basal-type breast cancer, Extracellular matrix, Apoptosis, Laminin-5

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Breast cancer: the matrix released

JCS 2005 118: 2102. [Full Text]  

This article has been cited by other articles:

				H. J. You, M. W. Bruinsma, T. How, J. H. Ostrander, and G. C. Blobe The type III TGF- receptor signals through both Smad3 and the p38 MAP kinase pathways to contribute to inhibition of cell proliferation Carcinogenesis, December 1, 2007; 28(12): 2491 - 2500. [Abstract] [Full Text] [PDF]