Decreased expression of SOCS-3 mRNA in breast cancer with lymph node metastasis

Abstract

Signal transducers and activators of transcription (STATs) play a pleomorphic role in signal transduction, similarly to an oncogene. Suppressors of cytokine signaling (SOCS) inhibit STAT pathways. In breast cancer, little is known about the correlation among STATs, SOCS, and clinicopathological/biological features. Therefore, we investigated p-STAT3 (activated form of STAT3) and SOCS-1/3 expression, and clarified their correlation. Immunohistochemical staining for p-STAT3 antigen was performed in 74 surgically resected primary breast cancers. Real-time RT-PCR was used to measure mRNA expression of SOCS-1 and SOCS-3. There were no significant correlations between p-STAT3 expression and clinicopathological/biological features. SOCS-3 mRNA expression in the lymph nodepositive group was significantly lower than that in the negative group (p=0.013). Among three groups divided based on the number of involved lymph nodes (node-negative group, 1-3 involved nodes group, 4 or more involved nodes group), the group with 4 or more involved nodes had the lowest expression of SOCS-3 (p=0.043). Correlations were not seen between SOCS-1 and SOCS-3 expression and other clinicopathological/biological features, except for blood vessel invasion. There were no statistical correlations between either SOCS-1 or SOCS-3 mRNA expression and p-STAT3 expression. Reduced expression of SOCS-3 is closely related to lymph node metastasis. Therefore, SOCS-3 may be a good predictor for lymph node metastasis.

Reduced inducibility of SOCS3 by interferon gamma associates with higher resistance of human breast cancer lines as compared to normal mammary epithelial cells

“…Reports of aberrant DNA methylation of SOCS genes in a number of breast cancer cell lines and tumors [29,30] have led to the suggestion that SOCS genes are silenced during oncogenic transformation of mammary tissue. In line with this supposition, decreased expression of SOCS3 has been positively correlated with increased metastatic potential in breast tumors [31]. On the other hand, constitutive expression of SOCS genes was reported in breast cancer lines [13] indicating absence of epigenetic transcriptional block.…”

Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma

“…As an established negative regulator of STATs, SOCS3 function has been examined in vitro and in vivo using diverse transformed cell lines. It has been identified that forced expression of SOCS3 resulted in growth inhibition of human lung adenocarcinoma A549 cells (He et al 2003) and lung cancer xenografts in nude mice (Nakagawa et al 2008). Mice deficient in SOCS3 die in utero as a consequence of uncontrolled leukemia inhibitory factor (LIF) signaling inactivation of the LIF receptor rescues the SOCS3-/-phenotype (Takahashi et al 2008;Roberts et al 2001).…”

Prognostic significance of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 expression in hepatocellular carcinoma

“…Their data further revealed that deficient expression of SOCS3 was significantly associated with lymph node metastasis, blood vessel invasion, expression of VEGF and Ki-67 and reduced disease-free survival, concordant with our study in HCC. Moreover, Nakagawa et al (29) demonstrated that decreased expression of SOCS3 mRNA was correlated with tumor lymph node metastasis in breast carcinoma. However, Yang et al (21) detected the expression of SOCS3 in 87 HCC patients and observed that 67.8% of HCC lesions showed moderate to very strong SOCS3 staining, and increased expression of SOCS3 was positively associated with tumor vascular invasion and poor patient OS.…”