Questioning the oncogenic role of ΔNp73α in different cell lines expressing p53 or not

Eleonora Marrazzo, Sergio Marchini, Sara Previdi, Massimo Broggini

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The recent finding that the 1p36.3 locus gene encodes an array of different p73 isoforms with apparently distinct and sometimes opposing cellular functions, might explain the difficulty in establishing the protein's role as tumor suppressor. Therefore we need to investigate the roles of each of these splicing variants in cellular functions when expressed alone or in combination with other family members, as well as the genetic background on which the proteins are expressed. We investigated, in two p53 null cell lines, the human SCLC line H1299 and a subline derived from the human colon carcinoma cell line HCT116 (HCT116/379.2), the effects of ΔNp73α overexpression on cell growth and the response to anticancer treatment. We generated three different clones overexpressing ΔNp73α under a tetracycline inducible promoter. Immunofluorescent staining and luciferase reporter assays confirmed that clones HCT116/ΔNA and H1299/ΔN7 and H1299/ΔN11 did express a functional, nuclear localized ΔNp73α protein. The stable overexpression of ΔNp73α protein did not confer any cell growth advantage. Doubling time of clones overexpressing ΔNp73α were comparable to counterparts not expressing it. Clonogenic assays showed that the cytotoxic activity of different DNA damaging agents, such as cDDP, UV light and doxorubicin, were comparable in clones expressing ΔNp73 or not. The overall data argue against an oncogenic role for this isoform. These findings are independent of the p53 status since they overlap with those previously obtained by our group in HCT116 cell lines, wild type for p53.

Original languageEnglish
Pages (from-to)794-803
Number of pages10
JournalCancer Biology and Therapy
Volume5
Issue number7
Publication statusPublished - Jul 2006

Fingerprint

Clone Cells
Cell Line
Protein Isoforms
Proteins
HCT116 Cells
Null Lymphocytes
Ultraviolet Rays
Growth
Tetracycline
Luciferases
Doxorubicin
Colon
Staining and Labeling
Carcinoma
DNA
Genes
Neoplasms

Keywords

  • ΔNp73α
  • p53
  • Tumor biology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Questioning the oncogenic role of ΔNp73α in different cell lines expressing p53 or not. / Marrazzo, Eleonora; Marchini, Sergio; Previdi, Sara; Broggini, Massimo.

In: Cancer Biology and Therapy, Vol. 5, No. 7, 07.2006, p. 794-803.

Research output: Contribution to journalArticle

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