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

BMC Cancer

Hyeong-Gon Moon⁴  Jae Kyo Yi⁴  Hee Sung Kim³  Hea Young Lee⁴  Kyung-Min Lee⁴  Minju Yi⁴  Sookyung Ahn⁴  Hee-Chul Shin²  Ji-hyun Ju¹  Incheol Shin¹  Wonshik Han⁴  Dong-Young Noh⁴ 

[1] Department of Life Science, College of Natural Science, Hanyang University, Seoul, Korea

[2] Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea

[3] Department of Pathology, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, Korea

[4] Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

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

Others  :  1080029
DOI  :  10.1186/1471-2407-12-585

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

【 摘 要 】

Background

The 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.

Methods

The 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.

Results

In 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.

Conclusion

Our 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】

   
2012 Moon et al.; licensee BioMed Central Ltd.

【 图 表 】

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