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Signal transducer and activator of transcription 3 (STAT3) is a key signaling molecule and a central cytoplasmic transcription factor, implicated in the regulation of growth. STATs comprise a family of seven proteins (STAT 1, 2, 3, 4, 5a, 5b, and 6) unique in their ability both to transducer extracellular signals and regulate transcription directly. STAT3 normally resides in the cytoplasm and is often constitutively activated in many human cancer cells and tumor tissues and has been shown to induce expression of genes involved in cell proliferation and survival. Constitutively activated STAT3 correlates with a more malignant tumor phenotype, resistance to chemotherapy and is also associated with decreased survival in some cancers. Recently, STAT3 has been implicated as a promising target for therapeutic intervention in cancer.
Soft tissue tumors comprise of a group of relatively rare, anatomically and histologically diverse neoplasms derived from tissues of mesodermal and ectodermal layer. Clinically, soft tissue tumors range from totally benign to highly malignant neoplasms. Many are of an intermediate nature, which typically implies aggressive local behavior with a low to moderate propensity to metastasize. The incidence of soft tissue tumors is low accounting for 1% of adult malignancies and 15% of pediatric malignancies. Mortality, on the other hand, is high; the average five-year survival rate is only 60%. Most soft tissue tumors arises de novo, but a small number originates in injured tissue such as scars or radiation-exposed areas. Sarcomas possess specific molecular characteristics and frequently present distinct diagnostic problems, and even many of the better-characterized tumors still lack reliable prognostic markers. New specific molecular genetic markers are expected to become increasingly useful in the clinical evaluation of such tumors. Although the contribution of STAT3 to epithelial cancers and hematologic malignancies has been described in detail, little is known on the role of STAT3 dysregulation in sarcomas. The overexpression of STAT3 and pSTAT3 (Tyr705) has been observed in human soft tissue tumor samples and the expression level increases with tumor grade progression. Expression of STAT3 and pSTAT3 was significantly associated with its clinicopathological parameters such as tumor grade (P < 0.001; P < 0.001), tumor location (P = 0.025; P = 0.027), plane of tumor (P = 0.011; P = 0.006), and tumor necrosis (P = 0.001; P = 0.002). Western blotting and RT-PCR analysis showed increased expression of STAT3 and p-STAT3 as grade of malignancy increased. These findings suggest that constitutive activation of STAT3 is an important factor related to carcinogenesis of human soft tissue tumors and is significantly associated with its clinicopathological parameters which may possibly have potential diagnostic implications.
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Expression of immunohistochemical markers, STAT3 (A, C, E) and p-STAT3 (B, D, F), in benign (A and B); intermediate (C and D); malignant (E and F) soft tissue tumors. The nuclei were counterstained with hematoxylin blue.
Representative ethidium bromide stained 2% agarose gel showing semiquantitative Reverse Transcriptase polymerase chain reaction (RT-PCR) analysis at different stages of soft tissue tumors v/s GAPDH (269 bp) Lane 1: benign soft tissue tumor; lane 2: intermediate soft tissue tumor; lane 3: malignant soft tissue tumor.
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