Sequence analysis of B7 homolog-1 predicted that the 290-amino acid type I transmembrane protein, which is 20% and 15% identical to B7-1 and B7-2, respectively, has immunoglobulin V-like and C-like domains and a 30-amino acid cytoplasmic tail.
NCBI Summary:
This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
Paracrine and autocrine regulation of EGF-like factors in cumulus oocyte complexes (COCs) and granulosa cells: key roles for prostanglandin synthase 2 (Ptgs2) and progesterone receptor (Pgr). Shimada M et al. The molecular bridges that link the LH surge with functional changes in cumulus cells that possess few LH receptors are being unraveled. Herein we document that EGF-like factors amphiregulin (Areg), epiregulin (Ereg) and betacellulin (Btc) are induced in cumulus oocyte complexes (COCs) by autocrine and paracrine mechanisms that involve the actions of prostaglandins (PGs) and progesterone receptor (PGR). Areg and Ereg mRNA and protein levels were reduced significantly in COCs and ovaries collected from prostagandin synthase 2 (Ptgs2) null mice and Pgr null (PRKO) mice at 4 h and 8 h post-hCG, respectively. In cultured COCs, FSH/forskolin induced Areg mRNA within 0.5 h that peaked at 4 h, a process blocked by inhibitors of p38MAPK (SB203580), MEK1 (PD98059) and PTGS2 (NS398) but not PKA (KT5720). Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF receptor tyrosine kinase inhibitor AG1478, PD98059 and NS398. PGE2 reversed the inhibitory effects of AG1478 on AREG induced expression of Areg but not Ptgs2, placing Ptgs2 downstream of EGF-R signaling. PMA and adenovirally expressed PGRA synergistically induced Areg mRNA in granulosa cells. In COCs AREG not only induced genes that impact matrix formation but also genes involved in steroidogenesis (StAR, Cyp11a1) and immune cell-like functions (Pdcd1, Runx1, Cd52). Collectively, FSH mediated induction of Areg mRNA via p38MAPK precedes AREG induction of Ptgs2 mRNA via ERK1/2. PGs acting via PTGER2 in cumulus cells provide a secondary, autocrine pathway to regulate expression of Areg in COCs showing critical functional links between G-protein coupled receptor and growth factor receptor pathways in ovulating follicles.
Expression regulated by
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Ovarian localization
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Dong H, Strome et al 2002 reported that tumor-associated B7-H1 promotes T-cell apoptosis and has a potential mechanism of immune evasion.
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells. Except for cells of the macrophage lineage, normal human tissues do not express B7-H1. In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas. The pro-inflammatory cytokine interferon-gamma upregulates B7-H1 on the surface of tumor cell lines. Cancer cell associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro, and the apoptotic effect of B7-H1 is mediated largely by one or more receptors other than PD-1. In addition, expression of B7-H1 on mouse P815 tumor increases apoptosis of activated tumor-reactive T cells and promotes the growth of highly immunogenic B7-1(+) tumors in vivo. These findings have implications for the design of T cell based cancer immunotherapy.
Izhar