RESUMO
BACKGROUND: Defective DNA repair capacity caused by inherited polymorphisms could be associated with cancer susceptibility. One of the major repair pathways is Nucleotide Excision Repair (NER). We investigated Xeroderma Pigmentosum complementation group C (XPC) polymorphisms (Lys939Gln, PAT) with the risk of prostate cancer. METHODS: 154 confirmed prostate cancer patients and 205 Benign Prostate Hyperplasia (BPH) controls were recruited in this survey. The genotypes were determined by PCR-Restriction Fragment Length Polymorphism (RFLP) method. RESULTS: Our results indicated that there were no significant differences between the BPH group and patient group for the XPC Lys939Gln in this pathway. However, deletion/insertion (D/I) and insertion/insertion (I/I) of XPC PAT polymorphism in this pathway could decrease the risk of prostate cancer and act as a protective factor. CONCLUSIONS: In this study, XPC Lys939Gln gene polymorphism was not associated with the risk of developing prostate cancer in Iranian patients. There are no association between different alleles of this polymorphism and grades and stages of tumors, but our results indicated the significant association between XPC PAT and reduction of prostate cancer risk in this group of patients. For more significant results, further samples are required.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fenótipo , Reação em Cadeia da Polimerase , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fatores de Proteção , Medição de Risco , Fatores de RiscoRESUMO
OCT4 is a master regulator of self-renewal in embryonic stem cells and can potentially encode two spliced variants, designated OCT4A and OCT4B. We have examined the expression pattern of these OCT4 isoforms in various human pluripotent and nonpluripotent cells. Our data revealed that whereas OCT4A expression is restricted to embryonic stem (ES) and embryonal carcinoma (EC) cells, OCT4B can be detected in various nonpluripotent cell types. Furthermore, we detected a novel OCT4 spliced variant, designated OCT4B1, that is expressed primarily in human ES and EC cells and is downregulated following their differentiation. We also found a significantly higher level of OCT4B1 expression in stage-specific embryonic antigen-3 (SSEA3)(+) compared with SSEA3(-) subpopulations of cultured ES cells. Taken together, our data demonstrated a distinctive expression pattern for OCT4 spliced variants in different cell types and highlight the necessity of defining the type of OCT4 when addressing the expression of this gene in different human cells.
Assuntos
Processamento Alternativo , Regulação da Expressão Gênica , Fator 3 de Transcrição de Octâmero/biossíntese , Fator 3 de Transcrição de Octâmero/genética , Células-Tronco Pluripotentes/metabolismo , Células-Tronco/metabolismo , Antígenos Glicosídicos Associados a Tumores/biossíntese , Diferenciação Celular , Linhagem Celular Tumoral , Células-Tronco Embrionárias/citologia , Éxons , Células HeLa , Humanos , Íntrons , Células K562 , Isoformas de Proteínas , Antígenos Embrionários Estágio-Específicos/biossínteseRESUMO
OCT-4 (also known as POU5F1) is a key regulator of self-renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Although OCT-4 has been introduced as a molecular marker for germ cell tumors, little is known about its expression in somatic cancers. Here, we have investigated the potential expression of OCT-4 in bladder cancer. We used semiquantitative RT-PCR to examine the expression of OCT-4 in 32 tumors, 13 apparently nontumor tissues taken from the margin of tumors and 9 normal urothelial tissues. The expression of OCT-4 at protein level was further determined by Western blotting and immunohistochemical (IHC) analysis. OCT-4 expression was detected in almost all examined tumors (31/32), but at much lower level (p<0.001) in some nonneoplastic samples (6/22). A significantly strong correlation of 0.6 has been observed between OCT-4 expression and the presence of tumors (p<0.001). Western blot analysis further confirmed the expression of OCT-4 in tumor biopsies. According to IHC results, OCT-4 is primarily localized in the nuclei of tumor cells, with no or low immunoreactivity in nontumor cells. Our study demonstrated, for the first time, the expression of OCT-4 in bladder cancer and a further clue to the involvement of embryonic genes in carcinogenesis.