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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >DeltaNp63 isoforms differentially regulate gene expression in squamous cell carcinoma: identification of Cox-2 as a novel p63 target.
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DeltaNp63 isoforms differentially regulate gene expression in squamous cell carcinoma: identification of Cox-2 as a novel p63 target.

机译：DeltaNp63亚型差异调节鳞状细胞癌中的基因表达：鉴定Cox-2为新型p63靶标。

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摘要

The p53 homologue p63 produces six different isoforms that are important in development of epithelial tissues and squamous cell carcinoma of the head and neck (SCCHN). In SCCHN, the expression of p63 isoforms is highly complex, with over-expression of DeltaNp63 and p63beta isoforms in many tumours. To date, little is known about the functions of different DeltaNp63 isoforms and elucidating the distinctive properties of DeltaNp63 isoforms will help to clarify how they influence tumour biology. By gene expression profiling of SCCHN cells over-expressing the DeltaNp63 isoforms we identified different effects of the three isoforms, with DeltaNp63beta being more effective at gene induction than DeltaNp63alpha and DeltaNp63gamma, whereas DeltaNp63gamma was most effective at repressing gene expression. Thus, tumours expressing even low levels of DeltaNp63beta or DeltaNp63gamma may have distinct clinicopathological characteristics important for metastasis and therapeutic response. Induction of cyclooxygenase-2 (Cox-2) was shown by each isoform and data were confirmed by independent quantitative RT-PCR and western blotting. No direct binding of DeltaNp63 to the Cox-2 promoter could be seen, neither could any evidence for Cox-2 induction as a consequence of activated NF-kappaB pathway responses be found. As Cox-2 is known to inhibit radiotherapy responses in SCCHN patients, data indicate an additional mechanism through which DeltaNp63 acts to promote cell survival and influence therapeutic response of SCCHN. MIAME-compliant data have been deposited in the MIAME Express database (Accession No. E-MEXP-1842).
机译：p53同源物p63产生六种不同的同工型，这些同工型对上皮组织和头颈部鳞状细胞癌（SCCHN）的发育很重要。在SCCHN中，p63亚型的表达非常复杂，在许多肿瘤中都有DeltaNp63和p63beta亚型的过表达。迄今为止，对不同的DeltaNp63亚型的功能了解甚少，阐明DeltaNp63亚型的独特特性将有助于阐明它们如何影响肿瘤生物学。通过过表达DeltaNp63亚型的SCCHN细胞的基因表达谱分析，我们发现了三种亚型的不同作用，其中DeltaNp63beta在基因诱导上比DeltaNp63alpha和DeltaNp63gamma更有效，而DeltaNp63gamma在抑制基因表达上最有效。因此，表达甚至低水平的DeltaNp63beta或DeltaNp63gamma的肿瘤可能具有对于转移和治疗反应重要的独特的临床病理特征。每种同工型均显示了环氧合酶2（Cox-2）的诱导，并通过独立的定量RT-PCR和Western blotting证实了数据。没有看到DeltaNp63与Cox-2启动子的直接结合，也没有发现由于激活的NF-κB通路反应而导致Cox-2诱导的任何证据。由于已知Cox-2会抑制SCCHN患者的放射治疗反应，因此数据表明DeltaNp63可通过其他机制来促进细胞存活并影响SCCHN的治疗反应。符合MIAME的数据已存储在MIAME Express数据库中（登录号E-MEXP-1842）。

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