RESUMEN
hPuf-A is a member of RNA-binding PUF family that regulates mRNA translation. Redistribution of hPuf-A from the nucleolus to the nucleoplasm upon genotoxic stress modulates the poly(ADP-ribosyl)ation activity of PARP-1. Here, we report a novel function of hPuf-A involved in promoting breast cancer progression. Immunohistochemical studies showed higher expression levels of hPuf-A in stage I, II, III, and IV breast cancer specimens in contrast with those of hPuf-A in ductal carcinoma in situ. The presence of hPuf-A is highly associated with colony formation capacities in breast cancer T47D and MDA-MB-231 cells. Xenograft growth of hPuf-A-silenced and hPuf-A overexpressing MDA-MB-231 cells in nude mice was substantially in concert with colony formation capacities. This promoting effect of hPuf-A in tumorigenesis might be correlated with the regulation of its associated mRNAs, such as RbAp48 and DDX3. Collectively, hPuf-A may have diagnostic values in breast cancer progression.
Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinogénesis/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Unión al ARN/genética , Animales , Neoplasias de la Mama/patología , Carcinogénesis/patología , Carcinoma Intraductal no Infiltrante/secundario , Línea Celular Tumoral , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Antígenos de Histocompatibilidad Menor , Estadificación de Neoplasias , Trasplante de Neoplasias , Proteínas de Unión al ARN/metabolismo , Carga Tumoral , Regulación hacia ArribaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of inhibitory and activating KIRs on a cohort of Chinese leukemia patients who received haplo-identical hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Donor's inhibitory and activating KIRs and recipient's HLA-C from 47 cases who received haplo-identical HSCT were tested by PCR-SSP. 2 year overall survival (OS), incidence of severe (grade III to IV) acute GVHD (aGVHD) and relapse rate (RR) were analyzed.</p><p><b>RESULTS</b>(1) According to Matched (M) vs Mis-Matched (MM) between donor's inhibitory KIR and recipient's HLA-C1/C2 subgroup, 2 year OS rate in M group [(87.5 +/- 8.3)%] was significantly higher than that in MM group (54.5 +/- 9.0)%, (P = 0.03). Lower incidence of relapse rate was seen in M group than in M/MM groups [0 vs (25.4 +/- 9.5)%, P = 0.05]. In 30 cases of myeloid leukemia patients, there was lower RR in M group than in MM groups [0 vs (35.0 +/- 14.4)%, P = 0.04]. (2) According to the 3 activating KIR genes: KIR2DS1/ KIR2DS2/ KIR2DS3, lower incidence of grade III-IV aGVHD was seen in KIR2DS1 (+) group than in KIR2DS1 (-) group (13% vs 28%, respectively, P > 0.05); and so was done in KIR2DS3 (+) group (11% vs 26%, respectively, P > 0.05). The RR was lower in KIR2DS2 (+) group [0% vs (17.3 +/- 7.1)%, respectively, P > 0.05].</p><p><b>CONCLUSIONS</b>In our haplo-identical HSCT setting, match between donor's inhibitory KIR and recipient's HLA-C can significantly reduce the incidence of relapse rate and improve OS. Although lower incidences of severe aGVHD are noted in the donors with KIR2DS1 (+) or KIR2DS3 (+), and lower relapse rate is noted in the donors with KIR2DS2 (+) but without statistic difference, no remarkable effects of activating KIRs on OS have been found in our relatively small clinical series.</p>