p63 and p73 Isoform Expression in Non-small Cell Lung Cancer and Corresponding Morphological Normal Lung Tissue

Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 5.28). 03/2011; 6(3):473-81. DOI: 10.1097/JTO.0b013e31820b86b0
Source: PubMed


The TP73 and TP63 genes are members of the p53 tumor suppressor family and are expressed in different N-terminal isoforms either with proapoptotic (transactivation domain, TA) and antiapoptotic (N-terminally truncated, ΔN) function. Unlike p53, the role of p73 and p63 in tumor is controversial. It has been recently hypothesized that altered ΔN:TA expression ratio, rather than single isoform overexpression, plays a role in the pathogenesis of many diseases, including lung cancer.
Isoform-specific, real-time polymerase chain reaction and immunohistochemistry analysis on matched cancer and corresponding normal tissues from surgically resected non-small cell lung cancers (NSCLCs) have been performed aiming to explore the expression levels of each p63 and p73 N-terminal isoforms and their ΔN:TA expression ratio.
For both p63 and p73, a N-terminal isoform-specific modulation that alter ΔN:TA isoform balance was identified. In particular, ΔNp63 isoform was significantly up-modulated, whereas TAp63 was slightly down-modulated in NSCLC specimens. Likewise, Δ2p73 and Δ2/3p73 were up-modulated, whereas ΔNp73 and ΔN'p73 isoforms were down-modulated. Moreover, a higher TAp63 and ΔN'p73 transcripts expression, detected in the normal tissue surrounding the tumors, correlates with poor patient outcome, representing independent prognostic factors for overall survival (ΔN'p73: p = 0.049, hazard ratio = 3.091, 95% confidence interval = 1.005-9.524 and TAp63: p = 0.001, hazard ratio = 8.091, 95% confidence interval = 2.254-29.05).
Our findings suggest that p63 and p73 altered ΔN:TA expression ratio occurs in NSCLC likely contributing to the molecular pathogenesis of this tumor.

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    • "Perhaps because it has so many functions and partners, TP53 is actually idiosyncratic in its regulation and the two probes designed to this gene lie in an small isolated graph component consisting of 3 transcripts (together with YWHAE a protein known to associated with P53). By contrast, the related TP73 gene is strongly enriched in bronchial epithelium (Cluster 11) and has been ascribed roles as a tumour suppressor in the lung [53]. More importantly, their analysis is based largely upon the limited perspective of yeast and/or the still limited information content of GO terms. "
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