Anti-apoptotic Role of Bcl-2-Associated Athanogene-3 Protein Overexpression in the Pathogenesis of Endometrial Cancers: An Aid for New Therapeutic Targets

Bcl-2相关凋亡基因3蛋白过表达在子宫内膜癌发病机制中的抗凋亡作用:为新的治疗靶点提供线索

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Abstract

OBJECTIVE: Bcl-2-associated athanogene-3 (BAG-3) is a cytoplasmic multidomain protein member that belongs to the BAG family of co-chaperones that are known to be involved in several cellular processes, including control of apoptosis, autophagy, and cytoskeletal dynamics. Normal tissues show weak to negligible expression as it is downregulated. However, its expression is upregulated in various epithelial and hematological malignancies, including endometrial, cervical, and chronic lymphoid leukemia. It plays a vital role in tumor cell proliferation, metastasis, and therapy resistance; thus, its expression has been determined to be a valuable tool in developing targeted therapeutic strategies. Endometrial cancers are one of the most common female genital tract malignancies with high mortality. Therefore, in this study, we evaluated the BAG-3 protein immunoexpression in 33 cases of endometrial cancer and correlated its expression with prognostic determiners. MATERIALS AND METHODS: We performed a retrospective study of BAG-3 immunoexpression in 33 cases of endometrial carcinoma. Cytoplasmic and membranous staining was considered positive and its correlations with prognostic factors such as myometrial invasion, LVSI, and ovarian involvement were analyzed. RESULTS: BAG-3 immunopositivity was seen in 31 (93.9%) cases and two cases were found to be negative. Twenty-two (66.6%) showed strong (3 +) intensity, seven (21.2%) showed moderate, and two (6.1%) showed weak BAG-3 immunostaining. No significant correlation was seen between grade and intensity. CONCLUSION: Inhibiting BAG-3 expression can induce apoptosis, thus promoting a new therapeutic target for the treatment of endometrial carcinoma.

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