Oncogene database

7161

TP73

tumor protein p73;TP73;tumor protein p73

p53-like transcription factor|p53-related protein

1p36.3

protein-coding

p73 and p63 are recently cloned genes that share considerable structural and functional homologies with the p53 tumor suppressor gene. These genes, unlike p53, express multiple mRNA isoforms with variable biologic functions, and their suppressor nature has yet to be confirmed. To determine the interrelationship between these genes in the tumorigenesis of head and neck squamous carcinoma (HNSC), we performed immunohistochemical analyses of their protein products and compared the data with clinicopathologic parameters in 38 patients. In histologically normal epithelium, p53 and p73 showed similar basal and/or parabasal expression, but that of p53 was weaker and discontinuous. p63 staining was noted in more suprabasal cellular layers and was stronger. In dysplasias, ALL three markers manifested variable but gradual increase in extent and intensity of cellular expression with histologic progression. In carcinomas, p63 was the most frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%). Significant statistical correlation was noted only between p63 and p73 expressions (P =.04). Although no statistical correlation was found between p53 and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73 expression was associated with distant metastasis and perineural/vascular invasion. Our study indicates that (1) p63 and p73 expression may represent an early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63 and p53 expression suggests an independent and/or compensatory functional role, (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may function as oncogenes in the development of these tumors.

OBJECTIVE: This study was designed to investigate the expression of p73 and Proliferating Cell Nuclear Antigen (PCNA) and their association with clinical, histologic characteristics and prognosis in LSCC. METHOD: p73 protein and PCNA protein were examined by using immunochistochemical SABC staining method in 65 cases of LSCC and in 23 adjacency carcinoma cases. RESULT: p73 protein and PCNA protein in LSCC shows stronger expression than that in adjacency carcinoma, which is statistically significant (P <0.05). p73 protein positive expression shows stronger in stage III approximately IVof LSCC than that in stage I approximately II (P<0.05); it more often appears in recurrent cases than in primary cases (P <0.05). And p73 protein positive expression with distant metastasis was stronger than that in LSCC without distant metastasis (P <0.05). PCNA protein positive expression was stronger in stage III approximately IV of LSCC than that in stage I approximately II (P <0.05); it more often appears in recurrent cases than in primary cases (P <0.05). PCNA protein positive expression more frequently appears in poor differentiation of LSCC, compared to well/mediate differentiation (P <0.05); PCNA positive expression in cases with cervical lymph node metastasis and distant metastasis was stronger than that without metastasis (P <0.05). PCNA expression had a significantly stronger in patients whose survival time over 5 years than that in patients whose survival time less than 5 years (P <0.05). Analysing with multivariate Cox, the expression of PCNA is an important marker of poor prognosis (RR= 2.43, P <0.05). CONCLUSION: p73 protein positive expression may play a part in LSCC progression and function as an oncogene in the development of LSCC. PCNA positive expression was closely linked with the risk of LSCC; it can be an important predictor on evaluating the prognosis of LSCC. There was positive correlation existing between p73 protein and PCNA protein expression in LSCC.

BACKGROUND: Differential mRNA splicing and alternative promoter usage of the TP73 gene results in the expression of multiple NH2-truncated isoforms that act as oncogenes. Abundant levels of these p73 variants in a variety of human cancers correlated with adverse clinical prognosis and response failure to conventional therapies, underscoring their relevance as marker for disease severity and target for cancer intervention. With respect to an equally important role for amino-truncated p73 splice forms (DeltaTAp73) and DeltaNp73 (summarized as DNp73) in the tumorigenic process, we designed locked nucleic acid (LNA) antisense oligonucleotide (ASO) gapmers against individual species that were complementary to DeltaEx2 and DeltaEx2/3 splice junctions and a region in exon 3B unique for DeltaN and DeltaN. RESULTS: Treatment of cancer cells with these ASOs resulted in a strong and specific reduction of tumorigenic p73 transcripts and proteins, importantly, without abolishing the wild-type p73 tumor suppressor form as observed with p73-shRNA. The specific antisense oligonucleotides rescued cells from apoptosis inhibition due to overexpression of their corresponding amino-truncated p73 isoform and decreased tumor cell proliferation. Furthermore, ASO-116 against DeltaEx2/3 coupled to magnetic nanobead polyethyleneimine (MNB/PEI) carriers significantly inhibited malignant melanoma growth, which correlated with a shift in the balance between endogenous TAp73 and DeltaEx2/3 towards apoptotic full-length p73. CONCLUSION: Our study demonstrates the successful development of LNA-ASOs that selectively differentiate between the closely related p73 oncoproteins, and provide new tools to further delineate their biological properties in different human malignancies and for therapeutic cancer targeting.

OBJECTIVE: To investigate the mRNA expression and promoter methylation status of p73 gene in the peripheral blood of children with Wilms tumor (WT), and their relationship. METHODS: Forty-five children with WT were selected as the case group, and 15 sex- and age- matched children (without malignancies) who visited the hospital for physical examination or other reasons were selected as the control group. Peripheral blood was collected from both groups. Real-time quantitative PCR and methylation-specific PCR were used to determine the mRNA expression level and promoter methylation status of p73 gene. Their relationship with clinicopathological features and the effect of promoter methylation on mRNA expression of p73 gene were analyzed in the case group. RESULTS: The relative quantity (RQ) of p73 mRNA in the case group was significantly higher than in the control group (3.2 +/- 0.9 vs 1.6 +/- 1.1; P<0.01). The positive rate of p73 gene promoter methylation in the case group was significantly lower than in the control group (20% vs 73%; P<0.01). In the case group, the RQ of p73 mRNA was significantly higher in children with methylated p73 gene promoter than in those with unmethylated p73 gene promoter (P<0.01). In children with methylated p73 gene promoter, the RQ of p73 mRNA was significantly higher in the case group than in the control group (P<0.01). In children with unmethylated p73 gene promoter, there was no significant difference in RQ of p73 mRNA between the case and control groups (P=0.810). CONCLUSIONS: Aberrant promoter methylation of p73 gene in peripheral blood is one of the gene expression regulations in children with WT, and it is related to the onset and development of WT. The p73 gene may play a role as oncogene in WT patients with p73 gene promoter methylation and mRNA overexpression is associated with promoter methylation status of p73 gene.