The Effects of WW2/WW3 Domains of Smurf2 Molecule on CD4+CD25+/CD4+ Proportion in Spleen of 4T1 Tumor Bearing BALB/c Mice

• Published in: Iranian biomedical journal Vol. 24; no. 4; pp. 214 - 219
• Main Authors: Mosayebzadeh Roshan, Hani, Abtahi-Eivary, Seyed-Hosein, Shojaee-Mend, Hassan, Mohammadzadeh, Alireza, Bahari Sani, Zahra
• Format: Journal Article
• Language: English
• Published: Iran Pasteur Institute of Iran 01.07.2020
• Subjects: Animals; Arginase; Bearing; Breast cancer; Carcinoma; CD25 antigen; CD4 antigen; CD4 Antigens - metabolism; CD4-Positive T-Lymphocytes - metabolism; Cell Line, Tumor; Cell Proliferation; Domains; Female; Flow cytometry; Full Length; Gene expression; Interleukin-2 Receptor alpha Subunit - metabolism; Mammary gland; Mice, Inbred BALB C; Protein Domains; Proteins; Signaling; Spleen; Spleen - metabolism; transforming growth factor-; Tumors; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - metabolism; ww domains; Arginase; Transforming growth factor-
• ISSN: 1028-852X; 2008-823X; 2008-823X
• DOI: 10.29252/ibj.24.4.214

TGF-β has long been considered as the main inducer of Tregs in tumor microenvironment and is the reason for the aberrant number of Tregs in tumor-bearing individuals. Recently, it has been suggested that the enzyme arginase I is able to mediate the induction of Tregs in a TGF-β-independent fashion. The recombinant WW2/WW3 domains from smad ubiquitination regulatory factor 2 molecule was demonstrated to increase TGF-β signaling while reducing arginase I gene expression. In this study, we aimed to examine the effects of this recombinant protein on CD4+CD25+/CD4+ proportion in the spleen of 4T1 mammary carcinoma-bearing BALB/c mice. Flow cytometry was used to evaluate CD4+CD25+ spleen cell populations of the tumor-bearing mice that received WW2/WW3 protein treatment and those of the control group. The results indicated a significant rise in CD4+CD25+/CD4+ ratio, along with an average increase in tumor mass of the subjects that underwent protein treatment. It can be inferred that the heightened CD4+CD25+/CD4+ proportion in the spleen of protein-treated tumor-bearing mice can be the result of the increased TGF-β signaling despite the reduced arginase I expression.