In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5724-5724
Abstract:
Despite a recent trend toward improvement, breast cancer (BC) mortality remains high due to resistance of recurrent tumors. A major cause of recurrence is likely a micro-metastatic seeding of cells that developed resistance by activating intrinsic or acquired survival pathways. In this regard, HER2 expression and cancer stem cells (CSCs) are the major cause for recurrence and targeting HER2 is well considered in therapeutic regiments. However, clinical data showed that anti-HER2 also benifit HER2−/low BC patients, suggesting that tumor cells may acquire HER2 gene activation to survive. We have previously reported that NF-κB mediates radioresistance by controlling HER2 gene. Herein, we identified HER2-expressing BC stem cells (HER2+/CD44+/CD24−/low) in radiation-resistant HER2−/low BC cells, MCF7/C6. Matrigel invasion, tumor sphere formation and radioresistance were enhanced in the HER2 mediating radioresistant cells. About 10% of the CD44+/CD24−/low cells sorted from MCF7/C6 cells or irradiated xenografts showed co-expression of HER2/CD44, ALDH and high tumorigenicity compared to HER2−/CD44+/CD24−/low cells, suggesting that the induction of HER2 expression further increased the BCSC aggressiveness. In fact, clinical data indicates that cells co-expressing HER2/CD44 were increased in recurrent tumors (84.6%) compared to the primary tumors (57.1%). Proteomics analysis identified a unique profile of proteins including DNA repair, mitochondrial function, redox, mTOR pathways that may govern the resistance of HER2+/CD44+/CD24−/low CSCs. These results demonstrate that HER2-mediated BC resistance can develop at the level of BCSC. Thus, HER2-expressing BCSCs may serve as an effective target to treat BC recurrence even from primary HER2−/low tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5724. doi:1538-7445.AM2012-5724
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-5724
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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