Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer

BMC Cancer

Research Article

Incheol Shin¹  Ji-hyun Ju¹  Hee Sung Kim²  Wonshik Han³  Jae Kyo Yi³  Minju Yi³  Dong-Young Noh³  Hea Young Lee³  Kyung-Min Lee³  Hyeong-Gon Moon³  Sookyung Ahn³  Hee-Chul Shin⁴ 

[1] Department of Life Science, College of Natural Science, Hanyang University, Seoul, South Korea;Department of Pathology, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, South Korea;Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea;Department of Surgery, Chung-Ang University College of Medicine, Seoul, South Korea;

关键词: Breast cancer;    P90RSK;    Chemotherapy;    Predictive marker;    ERK;    Estrogen receptor;   

DOI  :  10.1186/1471-2407-12-585

 received in 2012-08-26, accepted in 2012-11-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe clinical implication of Ras/Raf/ERK pathway activity in breast cancer tissue and its association with response to chemotherapy is controversial. We aimed to explore the value of p90RSK phosphorylation, a downstram molecule of the pathway, in predicting chemotherapy response in breast cancer.MethodsThe expression of phosphorylated p90RSK (phospho-p90RSK) and chemotherapy response was measured in 11 breast cancer cell lines and 21 breast cancer tissues. The predictive value of phospho-p90RSK was validated in core needle biopsy specimens of 112 locally advanced breast cancer patients who received anthracycline and taxane-based neoadjuvant chemotherapy.ResultsIn 11 breast cancer cell lines, the relative expression of phospho-p90RSK was inversely correlated with cell survival after doxorubicin treatment (p = 0.021). Similar association was observed in fresh tissues from 21 breast cancer patients in terms of clinical response. In paraffin-embedded, formalin-fixed tissues from core needle biopsy tissues from 112 patients, positive phospho-p90RSK expression was associated with greater tumor shrinkage and smaller post-chemotherapy tumor size. The association between phospho-p90RSK expression and chemotherapy response was more evident in estrogen receptor(ER)-positive tumors. The expression of phosphor-p90RSK did not show a significant relationship with the incidence of pCR. P90RSK silencing using siRNA did not affect the cancer cell’s response to doxorubicin, and the expression of phospho-p90RSK was highly correlated with other Ras/Raf/ERK pathway activation.ConclusionOur results suggest that phospho-p90RSK expression, which reflects the tumor’s Ras/Raf/ERK/p90RSK pathway activation can be a potential predictive marker for chemotherapy response in ER-positive breast cancer which needs further independent validation.

【 授权许可】

Unknown   
© Moon et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.