9021

SOCS3

suppressor of cytokine signaling 3;SOCS3;suppressor of cytokine signaling 3

STAT-induced STAT inhibitor 3|cytokine-inducible SH2 protein 3

17q25.3

protein-coding

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 node-positive 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.

Cytokine-induced expression of suppressors of cytokine signalling (SOCS) molecules is important for the negative feedback control of STAT-dependent cytokine signalling. The aim of this study was to investigate possible association between the promoter region polymorphisms of the SOCS3 gene and metastatic colorectal carcinoma in a Turkish population. The DNA samples obtained from 103 patients and 109 healthy individuals were analyzed by polymerase chain reaction/single-strand conformation polymorphism (SSCP), and nucleotide sequence analysis. Five sets of primers designed for the SOCS3 gene were used, and we did not detect significant differences in genotype frequencies for any of these polymorphisms between the study groups. Only the S3P1 region showed polymorphism and displayed three (1,2,4, 2,3,4 and 2,4) genotypes. Interestingly, 2,3,4 genotype was observed in 3 patients, but not in controls. Moreover, the sequence analysis revealed that the nucleotides positioned at -914 and -1031 nt had the polymorphisms. Nucleotide sequence analysis of SSCP band 1 and band 3 revealed C-914A (rs12953258) and T-1031C (rs111033850) polymorphisms, respectively. The T-1031C polymorphism lies in the border of the STAT-binding site. The T-1031C polymorphism (rs111033850) is a newly identified single nucleotide polymorphism with this study, and we submitted this to the NCBI database. However, these results suggested that there is no marked association between SOCS3 gene promoter region polymorphisms and the risk of developing metastatic colorectal cancer.

Suppressor of cytokine signaling-3 (SOCS-3), a multifunctional cytokine, is able to inhibit cell growth and migration by blocking the Janus kinase signal transducers and activators of transcription signaling (JAK/STAT) activation in oncogenesis. Although the STAT-3 expression was associated with lymph node metastasis from gastric cancer (GC), the implication of SOCS-3 expression in GC is not clearly elucidated. In this study, SOCS-3, STAT-3, and pSTAT-3 were evaluated in GC tissues and adjacent non-tumor tissues of 107 patients who underwent curative surgery by immunohistochemistry. Further, SOCS-3 and STAT-3 mRNA levels were also detected simultaneously. In addition, survival analysis was performed between clinicopathologic variables and prognosis of GC patients. Finally, correlative analysis was adopted for demonstration the best predicator of the survival independent factor. From the results, we demonstrated that only the lymph node metastasis was the independent predictor of the overall survival (OS) of GC patients, although SOCS-3, STAT-3, and other variables were significantly relative to OS. With multivariate logistical regression analysis, SOCS-3, STAT-3, and the status of extragastric nodal metastasis were identified to be the independent factors of the lymph node metastasis from GC. Ultimately, the SOCS-3 was the best predicator of lymph node metastasis from GC identified with the nominal regression analysis. Therefore, SOCS-3 should be considered as a potential indicator for prediction the lymph node metastasis from GC.