TY - JOUR
T1 - Combination E2F-1 and p53 gene transfer does not enhance growth inhibition in human squamous cell carcinoma of the head and neck
AU - Frank, Douglas K.
AU - Liu, Ta Jen
AU - Frederick, Mitchell J.
AU - Clayman, Gary L.
PY - 1998/9
Y1 - 1998/9
N2 - Ample data exist contending that wild-type p53 and E2F-1 cooperate to mediate apoptosis, that E2F-1-mediated apoptosis is p53 dependent in some situations, and that E2F-1 can induce accumulation of p53 in mammalian cells. These data support the Investig. of the biological consequences of combined wild-type p53 and E2F-1 overexpression in human squamous cell carcinoma of the head and neck (SCCHN) for the purpose of developing apoptosis-inducing molecular intervention strategies for the management of this devastating disease. The recombinant adenovirus (Ad) vectors Ad-p53 and Ad-E2F-1 were used for wild-type p53 and E2F-1 gene transfers, respectively, into SCCHN cell lines TU138 and TU167. SCCHN cells transduced with either p53, E2F-1, or both underwent in vitro growth analysis, which revealed that simultaneous p53 and E2F-1 gene transfer did not result in enhanced growth inhibition. To explain our growth assay findings on the basis of potential negative molecular interactions between E2F-1 and p53, Western and Northern blotting analyses were performed to investigate the differential expression of the downstream p53-transactivated genes, p21(WafI) and BAX, under various p53 and E2F-1 gene transfer conditions. Whereas Western immunoblotting demonstrated that E2F-1 antagonized p53 induction of p21(WafI) and BAX, Northern blotting revealed that this interference was pretranslationally regulated and p53 dependent. Coimmunoprecipitation assay confirmed that the wild-type p53 and E2F-1 gene products formed protein-protein complexes in our cell lines. Our in vitro data demonstrated that in SCCHN, E2F-1 interferes with induction of p53-transactivated genes, probably through the formation of protein-protein complexes. Simultaneous p53 and E2F-1 gene transfer is not therapeutically advantageous in this in vitro model of SCCHN.
AB - Ample data exist contending that wild-type p53 and E2F-1 cooperate to mediate apoptosis, that E2F-1-mediated apoptosis is p53 dependent in some situations, and that E2F-1 can induce accumulation of p53 in mammalian cells. These data support the Investig. of the biological consequences of combined wild-type p53 and E2F-1 overexpression in human squamous cell carcinoma of the head and neck (SCCHN) for the purpose of developing apoptosis-inducing molecular intervention strategies for the management of this devastating disease. The recombinant adenovirus (Ad) vectors Ad-p53 and Ad-E2F-1 were used for wild-type p53 and E2F-1 gene transfers, respectively, into SCCHN cell lines TU138 and TU167. SCCHN cells transduced with either p53, E2F-1, or both underwent in vitro growth analysis, which revealed that simultaneous p53 and E2F-1 gene transfer did not result in enhanced growth inhibition. To explain our growth assay findings on the basis of potential negative molecular interactions between E2F-1 and p53, Western and Northern blotting analyses were performed to investigate the differential expression of the downstream p53-transactivated genes, p21(WafI) and BAX, under various p53 and E2F-1 gene transfer conditions. Whereas Western immunoblotting demonstrated that E2F-1 antagonized p53 induction of p21(WafI) and BAX, Northern blotting revealed that this interference was pretranslationally regulated and p53 dependent. Coimmunoprecipitation assay confirmed that the wild-type p53 and E2F-1 gene products formed protein-protein complexes in our cell lines. Our in vitro data demonstrated that in SCCHN, E2F-1 interferes with induction of p53-transactivated genes, probably through the formation of protein-protein complexes. Simultaneous p53 and E2F-1 gene transfer is not therapeutically advantageous in this in vitro model of SCCHN.
UR - http://www.scopus.com/inward/record.url?scp=0031670757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031670757&partnerID=8YFLogxK
M3 - Article
C2 - 9748148
AN - SCOPUS:0031670757
SN - 1078-0432
VL - 4
SP - 2265
EP - 2272
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -