RESUMEN
Human homologue of polypyrimidine tract binding protein (PTB), a possible autoantigen for cancer-associated retinopathy (CAR), was isolated from a human retinal cDNA library. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue and has a 75% homology to the human PTB. The human PTBLP had four RNA recognition motifs (RRMs) and had a RNA binding ability. There are four splicing variants in PTBLP. The CAR serum recognized the full length form of PTBLP and the antigenic determinant was localized within 12 amino acids of the C-terminal region. The sequence was included in the fourth RRM sequence.
Asunto(s)
Autoantígenos/aislamiento & purificación , Clonación Molecular , Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Proteínas de Unión al ARN/aislamiento & purificación , Retina/inmunología , Enfermedades de la Retina/inmunología , Ribonucleoproteínas/aislamiento & purificación , Secuencia de Aminoácidos/genética , Autoantígenos/química , Autoantígenos/genética , ADN Complementario/aislamiento & purificación , Epítopos/inmunología , Femenino , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Síndromes Paraneoplásicos del Sistema Nervioso/metabolismo , Síndromes Paraneoplásicos del Sistema Nervioso/fisiopatología , Proteína de Unión al Tracto de Polipirimidina , Isoformas de Proteínas/genética , Estructura Terciaria de Proteína/genética , ARN Mensajero/aislamiento & purificación , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética , Retina/metabolismo , Retina/fisiopatología , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/fisiopatología , Ribonucleoproteínas/química , Ribonucleoproteínas/genética , Homología de Secuencia de Ácido NucleicoRESUMEN
Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration and also one of the paraneoplastic neurologic disorders. Sera of CAR patients usually contain high titers of antibodies against retinal proteins, and CAR is believed to be an autoimmune disease. Using serum from a CAR patient as a molecular probe, a homologue of the polypyrimidine tract-binding protein (PTB) was isolated from a cDNA library of rat neonatal retina. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue protein and has 73.5 and 68.8% homology with PTB and with a regulator of differentiation 1, respectively. Functional domains in the PTB, such as nuclear localization signals and four RNA recognition motifs (RRMs), were highly conserved. The expression of PTBLP mRNA was observed in the retina and brain but not in liver, kidney, spleen, or lung. The expression of PTBLP protein in rat retina was distributed in most of the cells in the ganglion cell layer and some cells in the inner nuclear layer. The PTBLP protein was localized in the nuclei of these cells. These results suggest that PTBLP is a new member of the PTB gene family and a neuron-specific homologue.
Asunto(s)
Proteínas del Ojo , Lipoproteínas , Proteínas del Tejido Nervioso , Proteínas de Unión al ARN/genética , Ribonucleoproteínas/genética , Secuencia de Aminoácidos , Animales , Antígenos de Neoplasias/inmunología , Secuencia de Bases , Sitios de Unión , Biomarcadores de Tumor/inmunología , Proteínas de Unión al Calcio/inmunología , Clonación Molecular , Femenino , Biblioteca de Genes , Hipocalcina , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteína de Unión al Tracto de Polipirimidina , Proteínas de Unión al ARN/inmunología , Ratas , Recoverina , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ribonucleoproteínas/inmunologíaRESUMEN
Comparative immunostaining with antibodies against gastric mucin and p53 was performed on 6 cases of minimal deviation adenocarcinoma (MDA) of the uterine cervix. The MDAs consisted of predominant areas of glands lined by extremely well-differentiated tall columnar epithelial cells with little cytological atypia and minor foci of less well-differentiated glandular epithelium with a minor degree of nuclear atypia. Immunostaining for gastric mucin with a monoclonal antibody HIK1083 revealed that all the tumors areas of typical MDA were partly immunoreactive for HIK1083, but the coexisting less well-differentiated glands were essentially negative. Four MDAs focally contained cells with p53 positive nuclei that were located exclusively in the less well-differentiated cells that lacked gastric mucin. In the pelvic lymph nodes in 2 cases, most of the metastatic tumor was less differentiated and a positive reaction for HIK1083 was observed only in small foci of typical MDA. No significant overexpression of p53 was observed in the metastases. Immunohistochemical expression of gastric mucin and p53 may be related to the histological differentiation of MDA, and detection of p53 overexpression may help to identify critical steps in the local progression of MDA.