Originally published as JCO Early Release 10.1200/JCO.2005.02.2350 on December 27 2005

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TAp73 Upregulation Correlates With Poor Prognosis in Human Tumors: Putative In Vivo Network Involving p73 Isoforms, p53, and E2F-1

From the Department of Medical Oncology, Hospital Universitario Puerta de Hierro; Department of Surgery, Hospital Universitario Puerta de Hierro; Department of Pathology, Hospital Santa Cristina, Madrid; and the Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain

Address reprint requests to Felix Bonilla, MD, PhD, Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/ San Martín de Porres, 4, 28035-Madrid, Spain; e-mail: felixbv{at}stnet.es

PURPOSE: Although full-length TAp73 variants largely mimic p53 suppressor activities, the transactivation-deficient transcripts TAp73 exert an oncogenic effect by inactivating p53 and TAp73 suppressor properties. Additionally, TAp73 may cooperate with oncogenic RAS to induce cell transformation, confer drug resistance, and induce the phosphorylation of phosphorylated Rb. Here, we study the expression of TAp73 and TAp73 variants and assess possible associations with E2F-1, p53 and K-ras status. We address the possible clinical relevance of alterations in these genes.

PATIENTS AND METHODS: We determine in 113 colon and 60 breast cancer patients (a) the expression levels of TAp73, TAp73 (Ex2p73, Ex2/3p73, and Np73), and E2F-1 transcripts by quantitative real-time reverse transcriptase polymerase chain reaction (PCR); (b) mutations in the first exon of K-ras by PCR–single-stranded confirmational polymorphism; and (c) p53 status by immunohistochemistry. Tumor characteristics were examined in each patient.

RESULTS: Both suppressor and oncogenic isoforms of TP73 were significantly coupregulated in tumor tissues. Associations were observed between (a) p53 wild type status and upregulation of some TP73 variants; (b) overexpression of E2F-1 and some TP73 forms; and (c) upregulation of TAp73 variants and advanced pathologic stage, lymph node metastasis, vascular invasion, presence of polyps, and tumor localization.

CONCLUSION: Overexpression of TP73 variants in tumor tissues indicates that they may be involved in colon and breast carcinogenesis. The association between upregulation of TAp73 isoforms and poor prognosis features, specifically advanced tumor stage, suggests that they may be of practical clinical prognostic value. Interestingly, the in vivo associations identified here may indicate a functional network involving p73 variants, p53, and E2F-1.

Supported by Instituto de Salud Carlos III Grant No. CP03/00032 and Spanish Ministry of Education and Science Grant No. 2004-01002.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author's contributions are found at the end of this article.

Related Correspondence

• p73 and p53 Pathway in Human Breast Cancers
  Cecilia Bozzetti, Rita Nizzoli, Antonino Musolino, Eugenia M. Martella, Pellegrino Crafa, Costanza A. Lagrasta, Roberta Camisa, Antonio Bonati, Paolo Lunghi, and Andrea Ardizzoni
  JCO 2007 25: 1451-1453 [Full Text]

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