Mutations in and Expression of the Tumor Suppressor Gene p53 in Egg-Type Chickens Infected With Subgroup J Avian Leukosis Virus

Abstract

To investigate the molecular mechanisms of the oncogenic effects of avian leukosis virus subgroup J (ALV-J), we examined mutations in and the expression of p53 in the myelocytomas distributed in the liver, spleen, trachea, and bone marrow, as well as in fibrosarcomas in the abdominal cavity and hemangiomas in skin from chickens that were naturally or experimentally infected with ALV-J. Two types of mutations in the p53 gene were detected in myelocytomas of both the experimentally infected and the naturally infected chickens and included point mutations and deletions. Two of the point mutations have not been reported previously. Partial complementary DNA clones with a 122-bp deletion in the p53 gene ORF and a 15-bp deletion in the C-terminus were identified in the myelocytomas. In addition, moderate expression of the mutant p53 protein was detected in the myelocytomas that were distributed in the liver, trachea, spleen, and bone marrow. Mutant p53 protein was not detected in the subcutaneous hemangiomas or in the abdominal fibrosarcomas associated with natural and experimental ALV-J infection, respectively. These results identify mutations associated with abnormal expression of p53 in ALV-J-associated myelocytomas, suggesting a role in tumorigenesis.Keywords subgroup J avian leukosis, egg-type chicken, tumor suppressor gene p53, mutation, retroviruses Avian leukosis virus subgroup J (ALV-J) induces myelocytomas, myeloid leukosis (ML), nephromas, fibrosarcomas, and other types of malignancies in chickens. 6 Recent studies have shown that the malignant transformation of normal cells and the occurrence and development of malignant tumors result from the abnormal structure, function, expression, and regulation of oncogenes and tumor suppressor genes. The physiological roles of the p53 gene include inducing apoptosis and differentiation of abnormal cells, protecting the integrity of the genome, and inhibiting tumor cell growth. The p53 gene is closely associated with the onset and development of tumors. Mutations in the p53 gene and the expression of mutant p53 protein may be used as indicators of malignant tumors.In the present study, we collected egg-type chickens that were suspected to be naturally infected with ALV-J and performed histopathologic analyses, isolated and identified the virus, and then experimentally infected specific pathogenfree (SPF) chickens with the isolated strain of the ALV-J virus. To determine whether p53 mutations were involved in the pathogenesis of chicken tumors resulting from exposure to ALV-J, we analyzed the molecular structure of the chicken p53 gene and the expression of the p53 protein. Here, we

Detection of p53 mutation and serum monitoring alert caused by Marek's disease virus

“…In the infected poultry, the mutation rate of p53 was 60 percent (12/20). Two types of mutations (deletions and point mutations) were detected in the p53, which was consistent with the results reported in previous studies [17]. In the 12 mutated p53 genes, the base sites with high mutation frequency were 651, 786, 828, 864 and 879.…”

“…The deleted sequence was located at 631-677 bp in the open reading frame of the reference sequence, resulting in missense mutations from the position 210 to the termination. The short form of p53 transcript was also found at the cases infected avian leukosis virus [17]. A series of missense mutations from the position 163 to the termination due to a base deletion were found in an experimentally infected chicken.…”

Detection of p53 mutation and serum monitoring alert caused by Marek's disease virus

“…In the infected poultry, the mutation rate of p53 was 60 percent (12/20). Two types of mutations, deletions and point mutations (single-point mutations and multiple-point mutations), were detected in the p53, which was consistent with the results reported in previous studies [22]. In the 12 mutated p53 genes, the base sites with high mutation frequency were 651, 786, 828, 864 and 879.…”

“…These mutations are mainly point mutations, which are frequently inactivated by base deletions and insertions; majority of p53 mutations are missense mutations [27]. In the current study, found after Qu's research [22]. In the present research, it is found that the p53 has high mutation frequency of 60% in poultry oncology, and the mutation region is mainly concentrated in the DBD.…”

Overexpression of p53 delivered using recombinant NDV induces apoptosis in glioma cells by regulating the apoptotic signaling pathway

“…Similar to various other cancers, the occurrence of glioma is associated with genetic mutations in p53 (20)(21)(22)(23)(24). The alteration or inactivation of p53 induced by mutations or its interaction with oncogene products of DNA tumor viruses may lead to cancer (25). Low p53 expression occurs in glioma, which leads to dysfunction of the p53-associated regulatory pathways (26).…”