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.
|Number of pages||10|
|Journal||Cancer Biology and Therapy|
|Publication status||Published - Jul 2006|
- Tumor biology
ASJC Scopus subject areas
- Cancer Research