Expression levels of p53 and p73 isoforms in stage I and stage III ovarian cancer.

The p53 gene has been investigated for its role in epithelial ovarian cancer but data collected until now are contradictory. The evidence that p53 belongs with p63 and p73 to a family of transcription factors re-opened interest in this gene family. Here, we used quantitative real time RT-PCR to determine expression levels of TAp53, TAp73 and their N-terminal splice variants in a cohort of 169 ovarian cancer patients with stage I and stage III disease. The TAp73 levels in stage III biopsies differed by 100-fold depending on the p53 status and overall survival appears to be significantly related to DeltaNp73 expression. Kaplan-Meyer analyses did not suggest a correlation between overall survival and levels of TAp73, DeltaNp73 or the DeltaNp73/TAp73 ratio. In conclusion, these data suggest that at least in our patient cohort p53 and p73 expression levels are not correlated to malignant progression of ovarian cancer. They might, however, play a role in tumour initiation.

[1]  G. Melino,et al.  p73: Friend or foe in tumorigenesis , 2002, Nature Reviews Cancer.

[2]  Tim Crook,et al.  Functional regulation of p73 and p63: development and cancer. , 2003, Trends in biochemical sciences.

[3]  F. Vikhanskaya,et al.  Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis. , 1998, Experimental cell research.

[4]  J. Pietenpol,et al.  p63: Molecular complexity in development and cancer. , 2004, Carcinogenesis.

[5]  A. Yang,et al.  Monoallelically Expressed Gene Related to p53 at 1p36, a Region Frequently Deleted in Neuroblastoma and Other Human Cancers , 1997, Cell.

[6]  S. Pilotti,et al.  p53 in drug resistance in ovarian cancer , 1997, The Lancet.

[7]  David P Lane,et al.  p53 isoforms can regulate p53 transcriptional activity. , 2005, Genes & development.

[8]  A. Yang,et al.  p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. , 1998, Molecular cell.

[9]  W. Deppert,et al.  A Novel Human p53 Isoform Is an Essential Element of the ATR-Intra-S Phase Checkpoint , 2005, Cell.

[10]  Xin Lu,et al.  Live or let die: the cell's response to p53 , 2002, Nature Reviews Cancer.

[11]  R. Zeillinger,et al.  Transdominant ΔTAp73 Isoforms Are Frequently Up-regulated in Ovarian Cancer. Evidence for Their Role as Epigenetic p53 Inhibitors in Vivo , 2004, Cancer Research.

[12]  U. Moll,et al.  p63 and p73: roles in development and tumor formation. , 2004, Molecular cancer research : MCR.

[13]  Xinbin Chen,et al.  ΔNp73β Is Active in Transactivation and Growth Suppression , 2004, Molecular and Cellular Biology.

[14]  D. Lane,et al.  p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress , 2006, Cell Death and Differentiation.

[15]  Pierre Hainaut,et al.  p53 protein variants: structural and functional similarities with p63 and p73 isoforms , 2004, Oncogene.

[16]  G. Wahl,et al.  Regulating the p53 pathway: in vitro hypotheses, in vivo veritas , 2006, Nature Reviews Cancer.

[17]  J. Bourdon,et al.  Expression of p53 isoforms in squamous cell carcinoma of the head and neck. , 2007, European journal of cancer.

[18]  E. Berns,et al.  TP53 and ovarian cancer , 2003, Human mutation.

[19]  S. Cannistra Cancer of the ovary. , 1993, The New England journal of medicine.

[20]  A. Contente,et al.  p53 induces the expression of its antagonist p73ΔN, establishing an autoregulatory feedback loop , 2002, Oncogene.

[21]  J C Reed,et al.  Association between cisplatin resistance and mutation of p53 gene and reduced bax expression in ovarian carcinoma cell systems. , 1996, Cancer research.

[22]  U. Moll,et al.  p53, p63 and p73--solos, alliances and feuds among family members. , 2001, Biochimica et biophysica acta.

[23]  A. Magliocco,et al.  A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors , 2003, Cancer.