Abstract
BackgroundTwo isoforms of Rho-associated coiled-coil kinase (ROCK), ROCKI and ROCKII, play an important role in many cellular processes. Despite the accumulating evidence showing that ROCK could be a potential cancer therapeutic target, the relevant tumor types to ROCK activation are not well clarified. The aim of this study was to evaluate the ROCK activation status in different tumor types of breast cancer.ResultsWe evaluated the immunoreactivities of phosphorylation-specific antibodies of ROCKI and ROCKII to inform their kinase activation in 275 of breast carcinoma tissues, including 56 of carcinoma in situ, 116 of invasive carcinoma, and 103 of invasive carcinoma with metastasis. ROCKII activation signal detected in nucleus was significantly correlated with tumor metastasis, while ROCKI and cytosolic ROCKII activation signals made no significant difference in that metastasis. Furthermore, nuclear ROCKII activation signal was associated with poor clinical outcome and correlated with late tumor stage, low expression of estrogen receptor (ER) and progesterone receptor (PR), overexpression of human epidermal growth factor receptor 2 (HER2) and high Ki67 labeling index.ConclusionsNuclear ROCKII activation signal might contribute to the tumor metastasis in breast cancer. Differences in ROCK activation that underlie the phenotypes of breast cancer could enhance our understanding for the use of ROCK inhibitors in cancer therapy.
Highlights
Two isoforms of Rho-associated coiled-coil kinase (ROCK), ROCKI and ROCKII, play an important role in many cellular processes
The percentage of tumor cells with perceptible ROCKII phosphorylation signal was evaluated, and the mean percentage of cells with nuclear signals was found to be significantly higher in invasive carcinoma with metastasis (ICM) cases (20.8 %) than in invasive carcinoma (IC) (8.7 %) and carcinoma in situ (CIS) (6.9 %) cases (P = 0.003)
ROCKI activation signal in nucleus was observed with no significant differences among CIS, IC or ICM cases (Table 2)
Summary
Two isoforms of Rho-associated coiled-coil kinase (ROCK), ROCKI and ROCKII, play an important role in many cellular processes. The aim of this study was to evaluate the ROCK activation status in different tumor types of breast cancer. We provided evidence that S1333 ROCKI and S1366 ROCKII phosphorylation can indicate their kinase active status in response to RhoA signaling [24, 25]. The kinase activation status of ROCKI and ROCKII in tissues could be evaluated directly by using these antibodies. The aim of this study was to evaluate the ROCKI and ROCKII activation status in different tumor types of breast cancer, including carcinoma in situ (CIS), invasive carcinoma (IC) and invasive carcinoma with metastasis (ICM), by immunohistochemical staining with anti-pS1333 ROCKI and anti-pS1366 ROCKII antibodies. The differences of ROCK activation status that underlie the phenotypes of breast cancer were assayed, and their associations with clinicopathologic factors and clinical outcome were characterized
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