The PRAME family of cancer testis antigens is essential for germline development and gametogenesis

Abstract

The precise mechanisms of the reproductive physiological processes, such as labor initiation, are poorly understood. Oxytocin (OT) is one of the well-known uterotonics and is clinically adopted as a medication to facilitate childbirth. Vasopressin (VP), a posterior pituitary hormone similar to OT, has also been proposed to be involved in the reproductive physiology. In this study, we found that a total deficiency of V1a receptor subtype (V1aR) in mice resulted in a reduced number of pups, delayed labor initiation, and increased post-delivery hemorrhage compared with those in wild-type mice. Among the VP receptor subtypes, only V1aR was found to be expressed in the murine uterus and its distribution pattern was different from that of the oxytocin receptor (OTR); V1aR expression was mainly distributed in the circular myometrium, whereas OTR was strongly expressed in both the circular and longitudinal myometrium. The maximum contractile force of the circular myometrium, induced by VP or OT, was attenuated in the pregnant uterus of Avpr1a-deficient mice. Contrarily, while OT expression was decreased in the Avpr1a-deficient uterus, OTR expression was significantly increased. These results suggest that V1aR deficiency not only reduces the uterine contractile force but also perturbs the expression of genes responsible for the reproductive physiology. Therefore, V1aR is necessary to exert the maximum contraction of the circular myometrium to deliver pups. This study revealed an important role of V1aR in physiological contraction and term parturition in mice.

PRAME Expression in Cancer. A Systematic Immunohistochemical Study of >5800 Epithelial and Nonepithelial Tumors

“…1 Physiologically, it acts as a repressor of retinoic acid receptor pathway and thereby regulates cell differentiation, growth, and apoptosis. 2,3 Because PRAME is recognized by tumor-reactive cytotoxic T cells, there may be rationale for anti-PRAME immunotherapy and need to assess PRAME immunopositivity in search of treatment targets. Currently, there are active phase I and II treatment trials for hematological malignancies and solid tumors involving vaccines and engineered T cells directed against PRAME (Clin-icalTrials.gov).…”

“…In a normal tissue, PRAME is expressed almost exclusively in the testis 1. Physiologically, it acts as a repressor of retinoic acid receptor pathway and thereby regulates cell differentiation, growth, and apoptosis 2,3. Because PRAME is recognized by tumor-reactive cytotoxic T cells, there may be rationale for anti-PRAME immunotherapy and need to assess PRAME immunopositivity in search of treatment targets.…”

The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas

“…PRAME is the founding member of a multi-gene family of CTAs. In gametogenic cells, the PRAME protein maintains pluripotency and regulates proliferation [ 44 , 45 , 46 ]. In the presence of retinoic acid, PRAME binds retinoic acid receptors (RAR) at retinoic acid response elements (RARE) [ 44 ].…”

Increasing Role of Targeted Immunotherapies in the Treatment of AML

“…The gene is located on the human chromosomal region 22q11, encodes a 509 amino acid (AS) protein and is recognized by the HLA-A24 receptor and subsequently presented to cytotoxic T cells (CTLs). The antigen is expressed in some healthy tissue; however, levels of expression in tumor tissue are highly increased, making the antigen an interesting target of immunotherapy [ 17 , 18 ].…”