A novel POU homeodomain gene specifically expressed in cells of the developing mammalian nervous system

Abstract

We report the isolation of a novel human POU domain encoding gene named RDC-1. The POU domain of the RDC-1 encoded protein is highly related to the POU domain potentially encoded by the rat brain-3 sequence and to that of the Drosophila I-POU protein; outside of the POU region, RDC-1 is unrelated to any previously characterized protein. The RDC-1 gene is expressed almost exclusively in normal tissues and transformed cells of neural origin. In the developing mouse and human fetus, RDC-1 is expressed in a spatially and temporally restricted pattern that suggests a critical role in the differentiation of neuronal tissues. In addition, RDC-1 is expressed in a unique subset of tumors of the peripheral nervous system including neuroepitheliomas and Ewing's sarcomas but not neuroblastomas. Based on its unique structural characteristics and expression pattern, we discuss potential functions for the RDC-1 protein.

EWS/ETS proteins promote expression and regulate function of the homeodomain transcription factor BRN3A

“…Expression in neural progenitor/NB hybrid ND7 cells is likely to derive from their progenitor component. Results previously describing BRN3A transcript expression in approximately 70% of EFT and derived cell lines but not in NB samples (Collum et al, 1992) correlate well with our findings.…”

“…BRN3A has been proposed to have an intact oncogenic function in EFT (Collum et al, 1992;Theil et al, 1993), and a potential positive correlation of BRN3A distribution in primary EFT samples with invasion (Table 1) (negative control) and GLI-1 (positive control) fragments in SKNMC cells using whole rabbit IgG or specific a-FLI-1 antibodies and amplification oligonucleotides as described in the Materials and methods section.…”

“…In addition, results from a study conducted before the discovery of EWS/ETS translocations in EFT suggested that BRN3A might be expressed in such tumors (Collum et al, 1992), and the BRN3A promoter is active in the Ewing's sarcoma cell line STA-ET-1 (Frass et al, 2002). In the mouse, Brn3a is expressed in specific post-mitotic neurons in the peripheral and central nervous systems (Fedtsova and Turner, 1995), and loss of many of these neurons in Brn3a-null mice indicates a critical requirement for Brn3a in some neuronal specification and survival (McEvilly et al, 1996;Xiang et al, 1996;Eng et al, 2001).…”

Brn-3a neuronal transcription factor functional expression in human prostate cancer

“…Expression of high levels of Brn-3a have previously been found in cervical, NE cancers and Ewing's sarcoma. [11][12][13] However, Brn-3a expression has only been compared to levels in corresponding noncancer tissue in cervical cancer, and found Brn-3 transcription factors in prostate cancer JKJ Diss et al to be upregulated. 11 Similar to the present study, overexpression of Brn-3a was found to increase cervical cancer cell growth in vitro and tumour growth in vivo.…”

“…4,10 Expression of these transcription factors has also been found to be altered in a number of different cancers in vitro and in vivo. Thus, Brn-3a levels are significantly elevated (mRNA, B300-fold; protein, B6-fold) in cervical cancers 11 and are also high in aggressive NE tumours including small-cell lung carcinomas, 12 Ewing's sarcoma and neuroepitheliomas; 13 Brn-3b is expressed at high levels in neuroblastoma 14,15 and teratocarcinoma cells 15 and its expression is upregulated in a subset of malignant breast cancers; 16 Brn-3c expression is reduced in small-cell (Merkel cell) carcinomas of the skin with poor prognosis. 17,18 Brn-3a, Brn-3b and Brn-3c genes share a common structure, composed of two exons separated by a short intronic sequence.…”