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Differential regulation of elafin in normal and tumor-derived mammary epithelial cells is mediated by CCAAT/enhancer binding protein beta.
Cancer Res. 2007 Dec 01; 67(23):11272-83.CR

Abstract

CCAAT/enhancer binding protein beta (C/EBP beta) is a transcription factor implicated in the control of development, differentiation, and proliferation of mammary epithelial cells. However, it remains unclear how C/EBP beta is involved in tumor suppression through its interaction with specific downstream genes in breast cancer. Tumor cells overexpress serine proteases, which play crucial roles in tumor invasion and metastasis. Elafin is an endogenous serine protease inhibitor and is transcriptionally down-regulated in most tumor cell lines. In this study, we show that C/EBP beta is differentially expressed in normal versus tumor cell lines and normal adjacent versus tumor tissues obtained from breast cancer patients. We identified elafin as a downstream effector of C/EBP beta and show that elafin is also differentially regulated between normal and tumor cells. The mechanism by which C/EBP beta regulates elafin expression is through its direct interaction with the elafin promoter. There are three C/EBP beta binding sites involved in the elafin promoter activity, and the overexpression of C/EBP beta transactivates the elafin gene through these sites in tumor cells. RNA interference studies in normal cells further evidenced the requirement of the C/EBP beta for the elafin expression and negative feedback loop between C/EBP beta and elafin. We suggest that elafin is a novel substrate of C/EBP beta, and alterations in C/EBP beta isoforms result in their differential binding to the elafin promoter, leading to the altered expression of the elafin between normal and tumor cells.

Authors+Show Affiliations

Department of Experimental of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18056453

Citation

Yokota, Tomoya, et al. "Differential Regulation of Elafin in Normal and Tumor-derived Mammary Epithelial Cells Is Mediated By CCAAT/enhancer Binding Protein Beta." Cancer Research, vol. 67, no. 23, 2007, pp. 11272-83.
Yokota T, Bui T, Liu Y, et al. Differential regulation of elafin in normal and tumor-derived mammary epithelial cells is mediated by CCAAT/enhancer binding protein beta. Cancer Res. 2007;67(23):11272-83.
Yokota, T., Bui, T., Liu, Y., Yi, M., Hunt, K. K., & Keyomarsi, K. (2007). Differential regulation of elafin in normal and tumor-derived mammary epithelial cells is mediated by CCAAT/enhancer binding protein beta. Cancer Research, 67(23), 11272-83.
Yokota T, et al. Differential Regulation of Elafin in Normal and Tumor-derived Mammary Epithelial Cells Is Mediated By CCAAT/enhancer Binding Protein Beta. Cancer Res. 2007 Dec 1;67(23):11272-83. PubMed PMID: 18056453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of elafin in normal and tumor-derived mammary epithelial cells is mediated by CCAAT/enhancer binding protein beta. AU - Yokota,Tomoya, AU - Bui,Tuyen, AU - Liu,Yanna, AU - Yi,Min, AU - Hunt,Kelly K, AU - Keyomarsi,Khandan, PY - 2007/12/7/pubmed PY - 2008/1/23/medline PY - 2007/12/7/entrez SP - 11272 EP - 83 JF - Cancer research JO - Cancer Res VL - 67 IS - 23 N2 - CCAAT/enhancer binding protein beta (C/EBP beta) is a transcription factor implicated in the control of development, differentiation, and proliferation of mammary epithelial cells. However, it remains unclear how C/EBP beta is involved in tumor suppression through its interaction with specific downstream genes in breast cancer. Tumor cells overexpress serine proteases, which play crucial roles in tumor invasion and metastasis. Elafin is an endogenous serine protease inhibitor and is transcriptionally down-regulated in most tumor cell lines. In this study, we show that C/EBP beta is differentially expressed in normal versus tumor cell lines and normal adjacent versus tumor tissues obtained from breast cancer patients. We identified elafin as a downstream effector of C/EBP beta and show that elafin is also differentially regulated between normal and tumor cells. The mechanism by which C/EBP beta regulates elafin expression is through its direct interaction with the elafin promoter. There are three C/EBP beta binding sites involved in the elafin promoter activity, and the overexpression of C/EBP beta transactivates the elafin gene through these sites in tumor cells. RNA interference studies in normal cells further evidenced the requirement of the C/EBP beta for the elafin expression and negative feedback loop between C/EBP beta and elafin. We suggest that elafin is a novel substrate of C/EBP beta, and alterations in C/EBP beta isoforms result in their differential binding to the elafin promoter, leading to the altered expression of the elafin between normal and tumor cells. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/18056453/Differential_regulation_of_elafin_in_normal_and_tumor_derived_mammary_epithelial_cells_is_mediated_by_CCAAT/enhancer_binding_protein_beta_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18056453 DB - PRIME DP - Unbound Medicine ER -