%0 Journal Article
%T C/EBPbeta-2 confers EGF-independent growth and disrupts the normal acinar architecture of human mammary epithelial cells
%A Linda Bundy
%A Sam Wells
%A Linda Sealy
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-43
%X We show that elevated C/EBPbeta-2 expression confers EGF-independent growth in MCF10A mammary epithelial cells. However, MCF10A cells expressing C/EBPbeta-3 are not EGF-independent, and high C/EBPbeta-3 or LIP expression is incompatible with growth. C/EBPbeta-2 overexpression disrupts the normal acinar architecture of MCF10A cells in basement membrane cultures and induces complex multiacinar structures with filled lumen, similar to the consequences of aberrant ErbB2 activation.Given the ability of C/EBPbeta-2 to confer EGF-independent growth to mammary epithelial cells as well as its capability for disrupting normal epithelial architecture and causing EMT, it is worth considering whether inhibitors which target ErbB family signaling pathways could be less effective in mammary epithelial cells with elevated nuclear C/EBPbeta-2 expression.The activation of tyrosine kinase receptors plays an important role in the genesis of breast cancer. From the extensive analysis of many breast tumors it is well established that ErbB tyrosine kinase receptors, in particular ErbB2 and ErbB1 (epidermal growth factor receptor, EGFR), often become constitutively active in breast cancer as a result of overexpression, or in the case of ErbB1, autocrine ligand production or mutation (for reviews see [1-4]). Approximately 25% of invasive breast cancers exhibit ErbB2 gene amplification and the rate of ErbB2 gene amplification or protein overexpression in ductal carcinoma in situ (DCIS) is the same or higher than in invasive cancers [2,3]. EGFR and ErbB2 co-overexpression in breast tumors is associated with resistance to endocrine therapies ([5,2] and references therein). Recognizing the alterations in EGFR family tyrosine kinase function galvanized the development of one of the first approved targeted cancer therapeutics, Herceptin, an antibody inhibitor of ErbB2 (reviewed in [6]). The success of Herceptin and other therapies targeting the ErbB receptor family in the treatment of breast canc
%U http://www.molecular-cancer.com/content/4/1/43