Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | BMC Cancer |
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| Online Access: | http://www.biomedcentral.com/1471-2407/12/585 |
| _version_ | 1830302648672190464 |
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| author | Moon Hyeong-Gon Yi Jae Kim Hee Lee Hea Lee Kyung-Min Yi Minju Ahn Sookyung Shin Hee-Chul Ju Ji-hyun Shin Incheol Han Wonshik Noh Dong-Young |
| author_facet | Moon Hyeong-Gon Yi Jae Kim Hee Lee Hea Lee Kyung-Min Yi Minju Ahn Sookyung Shin Hee-Chul Ju Ji-hyun Shin Incheol Han Wonshik Noh Dong-Young |
| author_sort | Moon Hyeong-Gon |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-19T09:10:05Z |
| format | Article |
| id | doaj.art-a6f81d0e173f4d34a5394b09f54c58b2 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-19T09:10:05Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-a6f81d0e173f4d34a5394b09f54c58b22022-12-21T20:28:14ZengBMCBMC Cancer1471-24072012-12-0112158510.1186/1471-2407-12-585Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancerMoon Hyeong-GonYi JaeKim HeeLee HeaLee Kyung-MinYi MinjuAhn SookyungShin Hee-ChulJu Ji-hyunShin IncheolHan WonshikNoh Dong-Young<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2407/12/585Breast cancerP90RSKChemotherapyPredictive markerERKEstrogen receptor |
| spellingShingle | Moon Hyeong-Gon Yi Jae Kim Hee Lee Hea Lee Kyung-Min Yi Minju Ahn Sookyung Shin Hee-Chul Ju Ji-hyun Shin Incheol Han Wonshik Noh Dong-Young Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer BMC Cancer Breast cancer P90RSK Chemotherapy Predictive marker ERK Estrogen receptor |
| title | Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer |
| title_full | Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer |
| title_fullStr | Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer |
| title_full_unstemmed | Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer |
| title_short | Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer |
| title_sort | phosphorylation of p90rsk is associated with increased response to neoadjuvant chemotherapy in er positive breast cancer |
| topic | Breast cancer P90RSK Chemotherapy Predictive marker ERK Estrogen receptor |
| url | http://www.biomedcentral.com/1471-2407/12/585 |
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