| First Author | Zatula N | Year | 2014 |
| Journal | Oncotarget | Volume | 5 |
| Issue | 16 | Pages | 6770-87 |
| PubMed ID | 25149534 | Mgi Jnum | J:310369 |
| Mgi Id | MGI:6762847 | Doi | 10.18632/oncotarget.2252 |
| Citation | Zatula N, et al. (2014) The BCL9-2 proto-oncogene governs estrogen receptor alpha expression in breast tumorigenesis. Oncotarget 5(16):6770-87 |
| abstractText | The majority of human breast cancers express estrogen receptor alpha (ER), which is important for therapy with anti-estrogens. Here we describe the role of BCL9-2, a proto-oncogene previously characterized as co-activator of Wnt/ss-catenin signaling, for mammary tumorigenesis in mice and human. ER positive human breast cancers showed overexpression of BCL9-2 and tamoxifen treated patients with high BCL9-2 demonstrated a better survival. BCL9-2 was upregulated during puberty and pregnancy in normal mammary epithelia, but downregulated in the involuted gland. BCL9-2 overexpression in vivo delayed the mammary involution and induced alveolar hyperplasia. Moreover, aged BCL9-2 transgenic mice developed ductal-like mammary tumors with high nuclear ER expression. We found, that primary cell cultures of BCL9-2 breast tumors responded to tamoxifen treatment. Moreover, BCL9-2 regulated the expression of ER and the proliferation of human breast cancer cells independently of ss-catenin. Finally, we describe a novel mechanism, how BCL9-2 regulates ER transcription by interaction with Sp1 through the proximal ESR1 gene promoter. In summary, BCL9-2 induces ER positive breast cancers in vivo, regulates ER expression by a novel ss-catenin independent mechanism in breast cancer cells, and might predict the therapy response to tamoxifen treatment. |
