Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer
- Authors
- Moon, Hyeong-Gon; Yi, Jae Kyo; Kim, Hee Sung; Lee, Hea Young; Lee, Kyung-Min; Yi, Minju; Ahn, Sookyung; Shin, Hee-Chul; Ju, Ji-hyun; Shin, Incheol; Han, Wonshik; Noh, Dong-Young
- Issue Date
- 10-Dec-2012
- Publisher
- BMC
- Keywords
- Breast cancer; P90RSK; Chemotherapy; Predictive marker; ERK; Estrogen receptor
- Citation
- BMC CANCER, v.12
- Journal Title
- BMC CANCER
- Volume
- 12
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/15933
- DOI
- 10.1186/1471-2407-12-585
- ISSN
- 1471-2407
- 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.
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