Relevance of Multiple Breast Cancer Cell Lines as Models for Breast Cancers
YJ Choi. Yale University School of Medicine, Bridgeport, CT
Background: Back ground: Breast cancer consists of a heterogenous population of cancer cells. Testing multiple breast cancer cell lines (BCC) would reflect the reasonably acceptable model of breast cancer in vivo. Most studies involve only a few BCC. Here, we tested 11 different pheno and geno-types of BCC focusing on ERβ expression together with breast cancer tissues as previous studies on ERβ have shown inconsistent results.
Design: BCC consisted of (1) MCF-7, T-47D, ZR-75 representing luminal epithelial-like cell type, (2) MDA-MB-361,MB 468, BT 474, MDA-MB-453, SK-BR-3 as weakly luminal epithelial-like type with Her-2 over expression, and (3) MDA-MB-231, Hs578T, BT-549 highly invasive, stromal/mesenchymal-like type. Tissue microarray sections of 11 BCC and 224 breast cancer tissues were tested for the expression of ERβ isoforms using three different clones (PG10, Dako;14C8,ABCAM ;AR385-5R, Biogenex) and also for ERα (ID5, Dako), Her-2 (HercepTest, Dako), PR, smooth muscle actin, vimentin, cyokeratin (AE1/AE3), and CK5/6 using the standard immunohistochemistry procedure after appropriate antigen retrieval and serum blocking. Over 5% nuclear or cytoplasmic expression was considered to be positive.
Results: Nine BCC except BT 549 and Hs578T maintained epithelial phenotype with positive cytokeratin. The luminal type, MCF-7 and T47D, ZR-75 were ERα+/PR+/Her-2-/cytokeratin + /vimentin- with high expression of ERβ. Five weakly luminal types were ERα-/PR+/Her-2 + /vimentin-/actin-/ERβ+ and 2 were ERα-/PR-/Her-2-/ERβ+/vimentin-/actin-. The stromal /mesenchymal type was ERα-/PR-/Her-2-/vimentin+/-/actin+/- with low ERβ expression. CK5/6 stain was seen only in MB 468. ERα and ERβ were co-expressed mostly in the luminal types. ERα negative and triple negative BCC showed low ERβ expression. In breast cancer tissues, ERβ was expressed in 55.4% (124/224) in all, and in 25 % (28/112) of ERα negative and 49% (29/61) of triple negative breast cancer tissues.
Conclusions: BCC lines with different pheno- and geno-types may reflect reasonably acceptable models to evaluate breast cancer cells in vivo. ERβ expression in BCC and breast cancer tissues were comparable. More specifically, BT-549, Hs578T, MDA-MB-231 can represent the mesenchymal type, 'epithelial–mesenchymal transition' type and MB 468 the basal-like type. Study are in progress to test RNA expression of ERβ isoforms with different agonist and antagonists to explore the targeted therapeutic potential of ERβ in ERα negative and Triple negative breast cancers.
Monday, March 22, 2010 1:00 PM
Poster Session II # 52, Monday Afternoon