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Open Access Research article

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

Hyeong-Gon Moon1, Jae Kyo Yi1, Hee Sung Kim2, Hea Young Lee1, Kyung-Min Lee1, Minju Yi1, Sookyung Ahn1, Hee-Chul Shin3, Ji-hyun Ju4, Incheol Shin4, Wonshik Han1 and Dong-Young Noh1*

  • * Corresponding author: Dong-Young Noh dynoh@snu.ac.kr

  • † Equal contributors

Author Affiliations

1 Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

2 Department of Pathology, Gachon University Gil Hospital, Gachon University of Medicine and Science, Incheon, Korea

3 Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea

4 Department of Life Science, College of Natural Science, Hanyang University, Seoul, Korea

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BMC Cancer 2012, 12:585  doi:10.1186/1471-2407-12-585

Published: 10 December 2012

Abstract

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.

Keywords:
Breast cancer; P90RSK; Chemotherapy; Predictive marker; ERK; Estrogen receptor