The role of the tumor suppressor p53 in spermatogenesis
Tim L. BeumerHermien L. Roepers‐GajadienIris S. GademanPaul PW van BuulGabriel Gil‐GómezD. H. RutgersDirk G. de Rooij
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P53 protein
P53 protein
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In an immunohistochemical investigation designed to study a mutated p53 protein in transitional-cell tumours (n = 44) we succeeded in identifying the presence of two types of transitional-cell tumours of human urinary bladder, such as p53 immunopositive and p53 immunonegative transitional-cell tumours. Thus, the results of the immunohistochemical investigation into the protein p53 were found out to directly correlate with the clinical course of transitional-cell tumours, that are held to be of great differential-diagnostic and prognostic significance.
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肿瘤 suppressor p53 在肿瘤抑制起一个枢轴的作用。p53 是在癌症的最经常变异的基因。作为 transcriptionfactor， p53 主要通过它的下游的目标 genes.Thus， p53 和它的目标基因形式的 transcriptional 规定在肿瘤抑制施加它的角色表明小径调整许多生物过程 toprevent tumorigenesis 的复杂 p53。最近的研究除了 apoptosis ，房间周期拘捕和老朽揭示了那，在新陈代谢和抗氧化剂防卫进一步在肿瘤 suppression.Studies 显著地贡献到它的角色的精力的规定的 p53'sfunctions 表演许多联系肿瘤的变异的 p53 蛋白质不仅失去肿瘤 wild-typep53 的镇压功能，而且获得独立于野类型的 p53 的新 oncogenic 活动包括支持肿瘤房间增长，幸存，新陈代谢的变化，野类型的 p53 功能的 frequentloss 和在肿瘤使 p53 成为的人的变异的 p53 的 gain-of-function 极其吸引人的 targetfor 癌症治疗。不同策略和许多小分子的药为基于 p53 的肿瘤 therapy.Here 正在被开发，我们在肿瘤开发在肿瘤抑制和 gain-of-function 异种 p53 考察 p53 的机制，也 asthe 在基于 p53 的肿瘤治疗的发展的最近的进展。
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The expression of the p53 tumor suppressor gene is tightly monitored, and this serves as a mechanism to ensure genomic stability prior to cells entering S-phase, and to make ensure that the protein is rapidly induced in response to DNA damage [1]. In addition to alterations in protein stability, it is generally accepted that regulation of the p53 protein levels is also controlled at the transcriptional level [1,2].
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To investigate the frequency of immunohistochemical expression of p53 protein in colorectal carcinomas; to evaluate the correlation between p53 alterations and the histopathological parameters; to determine the prognostic significance of this tumor marker. PATIENT POPULATIONS: Fourty patients with colorectal carcinomas.Paraffin embedded normal and tumoral tissues, stained, with HES, PAS, PAS-Alcian Blue stains. For detecting the p53 protein, a three step (streptavidin-biotin immunoperoxidase) immunohistochemical method was used.28 out of 40 (70%) colorectal carcinomas were positive for p53. The identification of nuclear accumulations of p53 protein in the present study was significantly correlated with the anatomic site and tumor stage.The mutational pattern observed in this study was substantially as expected. The p53 overexpression is present in advanced stage, thus demonstrating the prognostic value of this marker.
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Mutations of p53 are found in the majority of human malignancies. The accumulated mutant p53 can be detected in tumor sections by immunohistochemical methods. The abnormal accumulation of the defective p53 protein can induce the host to develop anti-p53 antibodies in sera of cancer patients. This study aimed to investigate the presence of anti-p53 antibodies in sera of patients with cholangiocarcinoma and to evaluate the correlation between such antibodies and p53 protein accumulation.The presence of serum anti-p53 antibodies in 49 patients with cholangiocarcinoma was determined by ELISA kit (Pharma Cell, France). Immunohistochemical detection of p53 protein expression was examined in available tissue samples of 36 patients.Serum anti-p53 antibodies were detected in 6 of 49 patients with cholangiocarcinoma (12.2%). Immunostaining of p53 was found in 15 of 36 patients (41.6%) and 4 of these 15 patients (26.7%) were positive for anti-p53 antibodies. The association between anti-p53 antibodies and p53 protein expression was statistically significant (P=0.023). No correlation was found between the presence of anti-p53 antibodies and sex, age, histological grade, site and stage of tumor (P>0.05).The majority of serum anti-p53 antibodies detected in cholangiocarcinoma were specifically associated with the accumulation of p53 protein in tumor tissues. However, antibody generation against the p53 protein is a relatively uncommon event in cholangiocarcinoma.
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In normal cells, p53 protei n is virtually unndetectable by immunohistochemical mathcds. Mutation of p53 gene results in overexpression of the protein and thus levels of p53 detectable by immunohistochemical methods. We studied the expression of p53 protein in humanCervical carcinoma (39 cases )paraffin embedded tissue sections by immunohistochemical methods.Of these cervical carcinorna specimens overexpression of P53 protein was showed in 19 cases (48.7 % )and was a higher percentage in low differentiation rodent cancer (75 % ) than in high differentiation rodent cancer (42. 9 % ). These results suggested that overexpression of p53 often occuredin cervical carcinoma and that the percentage of overexpression of p53 Was tight relative to thedifferentiation degree of human cervical carcinoma.
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