RESUMEN
Estrogen-related receptor (ERR)α presents structural similarities with estrogen receptor (ER)α. However, it is an orphan receptor not binding to naturally occurring estrogens. This study was designed to investigate the role of ERRα in endometrial cancer progression. Immunohistochemistry analysis on 50 specimens from patients with endometrial cancer showed that ERRα was expressed in all examined tissues and the elevated expression levels of ERRα were associated with advanced clinical stages and serous histological type (p < 0.01 for each). ERRα knockdown with siRNA suppressed angiogenesis via VEGF and cell proliferation in vitro (p < 0.01). Cell cycle and apoptosis assays using flow cytometry and western blot revealed that ERRα knockdown induced cell cycle arrest during the mitotic phase followed by apoptosis initiated by caspase-3. Additionally, ERRα knockdown sensitized cells to paclitaxel. A significant reduction of tumor growth and angiogenesis was also observed in ERRα knockdown xenografts (p < 0.01). These findings indicate that ERRα may serve as a novel molecular target for the treatment of endometrial cancer.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Endometriales/patología , Receptores de Estrógenos/biosíntesis , Animales , Neoplasias Endometriales/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Ratones , Neovascularización Patológica/metabolismo , Receptores de Estrógenos/análisis , Receptor Relacionado con Estrógeno ERRalfaRESUMEN
To investigate the clinical significance of ALDH2 genetic polymorphisms in cervical carcinogenesis. ALDH2 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 195 cervical smear in exfoliated cervical cell samples using Real-Time polymerase chain reaction (PCR) System. The frequency for the AG+AA genotype was seven in the normal group (70.0 %), 16 in the LSIL group (57.1 %), and 27 in the HSIL group (90.0 %). A significant difference was found between the LSIL and HSIL groups (P = 0.0064). Patients with HSIL lesions frequently had high-risk HPV infections and concurrently belonged to the AG+AA group. ALDH2 genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population.
Asunto(s)
Aldehído Deshidrogenasa Mitocondrial/genética , Estudios de Asociación Genética , Polimorfismo Genético/genética , Neoplasias del Cuello Uterino/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Papillomaviridae/clasificación , Riesgo , Factores de Riesgo , Neoplasias del Cuello Uterino/virologíaRESUMEN
The aim of the study is to investigate the clinical significance of glutathione-S-transferase GSTM1, GSTT1, and NQO1 c.609C>T (rs1800566) genetic polymorphisms in cervical carcinogenesis. GSTM1, GSTT1, and NQO1 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 192 cervical smear in exfoliated cervical cell samples using polymerase chain reaction (PCR) system and real-time polymerase chain reaction (PCR) system. The 19 patients with high-grade squamous intraepithelial lesion had statistically higher frequency of null GSTT1 genotype than 9 with low-grade squamous intraepithelial lesion (LSIL) among the 67 patients with high-risk HPV (P = 0.024). The 24 patients with HSIL had also statistically higher frequency of NQO1 (CT+TT) genotype than 14 with LSIL among the 67 patients with high-risk HPV (P = 0.024). GSTT1 null and NQO1 genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population.
Asunto(s)
Carcinogénesis/genética , Glutatión Transferasa/genética , NAD(P)H Deshidrogenasa (Quinona)/genética , Polimorfismo Genético/genética , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Neoplasias del Cuello Uterino/genética , Pueblo Asiatico , Femenino , Estudios de Asociación Genética , Técnicas de Genotipaje/métodos , Humanos , Papillomaviridae , Lesiones Precancerosas/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la Enfermedad , Neoplasias del Cuello Uterino/virologíaRESUMEN
It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.