CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5
Open Access
- 1 November 2005
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 118 (21), 5005-5022
- https://doi.org/10.1242/jcs.02616
Abstract
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 α3-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 α-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 α3-chain expression, and (3) enhancement of reconstituted ECM-mediated growth regulation and apoptosis. Similarly, suppression of laminin-5 α3-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 α3-chain expression. Results in these studies may provide insight into early events in basal-type mammary carcinogenesis.Keywords
This publication has 63 references indexed in Scilit:
- Expression of luminal and basal cytokeratins in human breast carcinomaThe Journal of Pathology, 2004
- Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast CancerJNCI Journal of the National Cancer Institute, 2003
- Integrin α3 expression as a prognostic factor in colon cancer: Association with MRP‐1/CD9 and KAI1/CD82International Journal of Cancer, 2001
- Cofactor Dynamics and Sufficiency in Estrogen Receptor–Regulated TranscriptionCell, 2000
- Differential Expression of the LAMB3 and LAMC2 Genes between Small Cell and Non-Small Cell Lung CarcinomasBiochemical and Biophysical Research Communications, 2000
- Inhibition of Retinoic Acid Receptor Function in Normal Human Mammary Epithelial Cells Results in Increased Cellular Proliferation and Inhibits the Formation of a Polarized Epitheliumin VitroExperimental Cell Research, 1997
- Preneoplastic transformation of human mammary epithelial cellsSeminars in Cancer Biology, 1995
- Apoptosis in the Pathogenesis and Treatment of DiseaseScience, 1995
- Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes.The Journal of cell biology, 1990
- The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells.The Journal of cell biology, 1990