BACKGROUND: Several biomarkers have been previously studied for breast cancer to define risk of recurrence and metastasis. Phosphatase of regenerating liver-3 (PRL-3) is one of them. High PRL-3 expression has been found to be correlated with axillary lymph node metastasis and survival in breast cancer. Herein, we evaluated the prognostic significance of PRL-3 expression and the relationship between PRL-3 and other clinicopathological factors. METHODS: PRL-3 expression was analyzed immunohistochemically in 122 invasive breast cancer tissues. We evaluated the correlation between PRL-3 and other clinicopathological factors by χ² test. Kaplan-Meier test and log rank method were used to define prognostic importance of PRL-3 expression. RESULTS: Of 122 breast cancer tumor samples, 46 (37.7 %) were negative while 76 (62.3 %) were positive in respect to PRL-3 expression. There was significant correlation between PRL-3 expression and other clinicopathological factors, such as histology, lymphovascular invasion (LVI), necrosis, progesterone receptor (PR) status, and the presence of triple negative disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared to tumors without LVI or necrosis (P = 0.05 and 0.03, respectively). Triple negative and cerb-B overexpressed breast cancers were found to be more positive PRL-3 expression than hormone receptor positive with cerb-B negative groups (luminal A) (P = 0.02).We could not find any relationship between PRL-3 expression and overall survival (OS) or disease-free survival (DFS) (P > 0.05). CONCLUSION: Although PRL-3 expression was related to LVI or necrosis which is important for tumor invasiveness, we could not find that PRL-3 as an important prognostic factor in breast cancer patients. In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group.
"Numerous correlative studies in tumors of the colon, stomach, breast, pancreas and ovaries have shown that PRL-3 expression increases with tumor progression (reviewed in , ). Further, PRL-3 expression also correlates with tumor clinicopathology and disease outcome in a variety of tumor types –. These correlative studies are supported by numerous functional studies (reviewed in , ). "
[Show abstract][Hide abstract] ABSTRACT: The metastasis-associated tyrosine phosphatase PRL-3/PTP4A is upregulated in numerous cancers, but the mechanisms modulating PRL-3 activity other than its expression levels have not been investigated. Here we report evidence for both Src-dependent tyrosine phosphorylation of PRL-3 and Src-mediated regulation of PRL-3 biological activities. We used structural mutants, pharmacological inhibitors and siRNA to demonstrate Src-dependent phosphorylation of endogenous PRL-3 in SW480 colon cancer cells. We also demonstrated that PRL-3 was not tyrosine phosphorylated in SYF mouse embryo fibroblasts deficient in Src, Yes and Fyn unless Src was re-expressed. Further, we show that platelet-derived growth factor (PDGF) can stimulate PRL-3 phosphorylation in a Src-dependent manner. Finally, we show that PRL-3-induced cell motility, Matrigel invasion and activation of the cytoskeleton-regulating small GTPase RhoC were abrogated in the presence of the phosphodeficient PRL-3 mutant Y53F, or by use of a Src inhibitor. Thus, PRL-3 requires the activity of a Src kinase, likely Src itself, to promote these cancer-associated phenotypes. Our data establish a model for the regulation of PRL-3 by Src that supports the possibility of their coordinate roles in signaling pathways promoting invasion and metastasis, and supports simultaneous use of novel molecularly targeted therapeutics directed at these proteins.
PLoS ONE 05/2013; 8(5):e64309. DOI:10.1371/journal.pone.0064309 · 3.23 Impact Factor
Qingqing He, Bo Peng, Dayong Zhuang, Lei Xiao, Luming Zheng, Ziyi Fan, Jian Zhu, Benmei Xu, Cheng Xu, Jiangman Zhao, Liming Wu, Peng Zhou, Lei Hou, Fang Yu, Guowei Zhao
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