Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
MetadataShow full item record
Phospholipase Cγ1 (PLCγ1) is highly expressed in several tumors. We have previously reported that both stable and inducible PLCγ1 down-regulation resulted in an almost complete inhibition of breast cancer-derived experimental lung metastasis formation. The aim of our study is to evaluate the association between the expression of PLCγ1 and of PLCγ1 phosphorylated at Tyr1253 (PLCγ1-pY1253) and at Tyr783 (PLCγ1-pY783) with the clinical outcome of patients with node negative, T1/T2 breast cancers. The study groups consisted of 292 (training set) and 122 (validation set) patients presenting with primary unilateral breast carcinoma (T1-T2), with no evidence of nodal involvement and distant metastases. PLCγ1, PLCγ1-pY1253 and PLCγ1-pY783 protein expression were assessed by immunohistochemistry on tissue microarrays and the results correlated with the clinical data using Kaplan–Meier curves and multivariate Cox regression analysis. Tumor cells while expressing variable proportions of cytoplasmic PLCγ1, express PLCγ1-pY1253 and PLCγ1-pY783 predominantly in the nucleus. High expression of PLCγ1, and of its activated forms, is associated with a worse clinical outcome in terms of incidence of distant metastases, and not of local relapse in T1-T2, N0 breast cancer patients undergone adjuvant chemotherapy. PLCγ1 over-expression appears to be a reliable predictive surrogate marker of development of metastases. Thus, targeting PLCγ1 pathways might represent a potential therapeutic approach for the prevention of metastatic disease in breast cancer.
Showing items related by title, author, creator and subject.
Class II phosphoinositide 3-kinase C2ß regulates a novel signaling pathway involved in breast cancer progression.Chikh, A.; Ferro, R.; Abbott, J.; Piñeiro, R.; Buus, R.; Iezzi, M.; Ricci, F.; Bergamaschi, D.; Ostano, P.; Chiorino, G.; Lattanzio, R.; Broggini, M.; Piantelli, M.; Maffucci, T.; Falasca, Marco (2016)It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical ...
Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinomaPrem Kumar, Alan; Loo, S.; Shin, S.; Tan, Tuan zea; Eng, C.; Singh, R.; Putti, T.; Ong, C.; Salto-Tellez, M.; Goh, B.; Park, J.; Thiery, J.; Pervaiz, S.; Clement, M. (2013)Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast ...
Shin, E.; Hay, H.; Lee, M.; Goh, J.; Tan, T.; Sen, Y.; Lim, S.; Yousef, E.; Ong, H.; Thike, A.; Kong, X.; Wu, Z.; Mendoz, E.; Sun, W.; Salto-Tellez, M.; Lim, C.; Lobie, P.; Lim, Y.; Yap, C.; Zeng, Q.; Sethi, G.; Lee, M.; Tan, P.; Goh, B.; Miller, L.; Thiery, J.; Zhu, T.; Gaboury, L.; Tan, P.; Hui, K.; Yip, G.; Miyamoto, S.; Kumar, Alan Prem; Tergaonkar, V. (2014)Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification ...