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Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer.
Clin Cancer Res. 2005 May 01; 11(9):3184-90.CC

Abstract

PURPOSE

CCAAT/enhancer binding proteins (C/EBP) are a family of transcription factors that regulate proliferation and differentiation in a variety of tissues. The purpose of this study was to explore the possibility that C/EBPalpha is involved in breast cancer.

EXPERIMENTAL DESIGN

We quantified C/EBPalpha mRNA expression levels in 24 primary breast tumors, 16 normal breast samples, and 8 breast cancer cell lines using quantitative real-time reverse transcription-PCR assay. C/EBPalpha protein levels were further determined by immunohistochemical analysis. To examine the consequence of C/EPBalpha expression in breast cancer, we stably transfected an inducible C/EPBalpha expression vector into three breast cancer cell lines.

RESULTS

Low expression of C/EBPalpha mRNA was found in 83% of primary breast cancer samples. Immunohistochemical study further showed either a markedly reduced or undetectable expression of C/EBPalpha protein in 30% of breast cancer specimens. The other 70% of breast cancers had C/EBPalpha expression in both the cytoplasm and nucleus; in control, C/EBPalpha was localized to the nucleus in the normal ductal cells. C/EBPalpha expression was associated with estrogen- and progesterone receptor-negative status. Induction of C/EBPalpha expression in these cell lines resulted in growth inhibition accompanied by G0-G1 cell cycle arrest and reduced anchorage-independent cell growth. C/EBPalpha expression was associated with down-regulation of c-myc and up-regulation of p21, PPARgamma, and the breast epithelial differentiation marker, maspin.

CONCLUSIONS

These results suggest that reduced expression of C/EBPalpha may play a role in the development and/or progression of breast cancer.

Authors+Show Affiliations

Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, USA. gerys@cshs.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15867211

Citation

Gery, Sigal, et al. "Down-regulation and Growth Inhibitory Role of C/EBPalpha in Breast Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 9, 2005, pp. 3184-90.
Gery S, Tanosaki S, Bose S, et al. Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer. Clin Cancer Res. 2005;11(9):3184-90.
Gery, S., Tanosaki, S., Bose, S., Bose, N., Vadgama, J., & Koeffler, H. P. (2005). Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(9), 3184-90.
Gery S, et al. Down-regulation and Growth Inhibitory Role of C/EBPalpha in Breast Cancer. Clin Cancer Res. 2005 May 1;11(9):3184-90. PubMed PMID: 15867211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer. AU - Gery,Sigal, AU - Tanosaki,Sakae, AU - Bose,Shikha, AU - Bose,Namrata, AU - Vadgama,Jay, AU - Koeffler,H Phillip, PY - 2005/5/4/pubmed PY - 2005/8/2/medline PY - 2005/5/4/entrez SP - 3184 EP - 90 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 9 N2 - PURPOSE: CCAAT/enhancer binding proteins (C/EBP) are a family of transcription factors that regulate proliferation and differentiation in a variety of tissues. The purpose of this study was to explore the possibility that C/EBPalpha is involved in breast cancer. EXPERIMENTAL DESIGN: We quantified C/EBPalpha mRNA expression levels in 24 primary breast tumors, 16 normal breast samples, and 8 breast cancer cell lines using quantitative real-time reverse transcription-PCR assay. C/EBPalpha protein levels were further determined by immunohistochemical analysis. To examine the consequence of C/EPBalpha expression in breast cancer, we stably transfected an inducible C/EPBalpha expression vector into three breast cancer cell lines. RESULTS: Low expression of C/EBPalpha mRNA was found in 83% of primary breast cancer samples. Immunohistochemical study further showed either a markedly reduced or undetectable expression of C/EBPalpha protein in 30% of breast cancer specimens. The other 70% of breast cancers had C/EBPalpha expression in both the cytoplasm and nucleus; in control, C/EBPalpha was localized to the nucleus in the normal ductal cells. C/EBPalpha expression was associated with estrogen- and progesterone receptor-negative status. Induction of C/EBPalpha expression in these cell lines resulted in growth inhibition accompanied by G0-G1 cell cycle arrest and reduced anchorage-independent cell growth. C/EBPalpha expression was associated with down-regulation of c-myc and up-regulation of p21, PPARgamma, and the breast epithelial differentiation marker, maspin. CONCLUSIONS: These results suggest that reduced expression of C/EBPalpha may play a role in the development and/or progression of breast cancer. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15867211/Down_regulation_and_growth_inhibitory_role_of_C/EBPalpha_in_breast_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15867211 DB - PRIME DP - Unbound Medicine ER -