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Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance.

Carastro LM, Lin HY, Park HY, Kim D, Radlein S, Hampton KK, Hakam A, Zachariah B, Pow-Sang J, Park JY - Prostate Cancer (2014)

Bottom Line: Methods.Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57-1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45-1.06, P = 0.09).Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Biochemistry & Physics, University of Tampa, Tampa, FL 33606, USA.

ABSTRACT
Background. Molecular markers for prostate cancer (PCa) risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP) in exon 2 of the p73 gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a p73 DNP allele. Methods. We investigated the association between p73 DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls. Results. Although we detected no association between p73 DNP and PCa risk, a significant inverse relationship between p73 DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31-0.99) was detected. Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57-1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45-1.06, P = 0.09). Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (P < 0.001). Conclusions. Our findings are consistent with an association between p73 DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

No MeSH data available.


Related in: MedlinePlus

Relative TAp73/ΔNp73 protein isoform ratios in cancer cell line lysates with GC/GC and GC/AT genotype. The TAp73/ΔNp73 protein isoform levels were determined from the western blotting data in Figures 2(a) and 2(b). These p73 protein isoform levels were used to calculate the relative ratio values reported in Table 3. The mean of TAp73/ΔNp73 protein isoform ratio values is box-plotted.
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fig3: Relative TAp73/ΔNp73 protein isoform ratios in cancer cell line lysates with GC/GC and GC/AT genotype. The TAp73/ΔNp73 protein isoform levels were determined from the western blotting data in Figures 2(a) and 2(b). These p73 protein isoform levels were used to calculate the relative ratio values reported in Table 3. The mean of TAp73/ΔNp73 protein isoform ratio values is box-plotted.

Mentions: We assessed the potential for a correlation between p73 protein isoform ratios and the p73 DNP genotype of cancer cell lines observed in cultured cancer cell lines. Genomic DNA samples were isolated from eleven cultured cell lines and the p73 DNP genotype was determined (Table 3). Total cellular protein samples were isolated from these cancer cell lines and subjected to p73 protein N-terminal isoform-specific western analyses for TAp73 and for ΔNp73, while blotting for actin in parallel as a protein loading control (Figures 2(a) and 2(b)). The TAp73 isoform, ΔNp73 isoform, and actin western blotting data were quantified using the ImageJ64 program. These values were used to calculate p73 protein N-terminal isoform ratios, in the form of TAp73/ΔNp73, relative to the actin control. Cancer cell line data were consistent with higher levels of TAp73 protein relative to ΔNp73 in the heterozygous cell lines compared to the wild type (Table 3 and Figure 3, P < 0.001). It was noteworthy that the only cancer cell line analyzed that was homozygous polymorphic for the p73 DNP, CaCO-2, contained no detectable p73 protein (Figure 2(b)).


Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance.

Carastro LM, Lin HY, Park HY, Kim D, Radlein S, Hampton KK, Hakam A, Zachariah B, Pow-Sang J, Park JY - Prostate Cancer (2014)

Relative TAp73/ΔNp73 protein isoform ratios in cancer cell line lysates with GC/GC and GC/AT genotype. The TAp73/ΔNp73 protein isoform levels were determined from the western blotting data in Figures 2(a) and 2(b). These p73 protein isoform levels were used to calculate the relative ratio values reported in Table 3. The mean of TAp73/ΔNp73 protein isoform ratio values is box-plotted.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109114&req=5

fig3: Relative TAp73/ΔNp73 protein isoform ratios in cancer cell line lysates with GC/GC and GC/AT genotype. The TAp73/ΔNp73 protein isoform levels were determined from the western blotting data in Figures 2(a) and 2(b). These p73 protein isoform levels were used to calculate the relative ratio values reported in Table 3. The mean of TAp73/ΔNp73 protein isoform ratio values is box-plotted.
Mentions: We assessed the potential for a correlation between p73 protein isoform ratios and the p73 DNP genotype of cancer cell lines observed in cultured cancer cell lines. Genomic DNA samples were isolated from eleven cultured cell lines and the p73 DNP genotype was determined (Table 3). Total cellular protein samples were isolated from these cancer cell lines and subjected to p73 protein N-terminal isoform-specific western analyses for TAp73 and for ΔNp73, while blotting for actin in parallel as a protein loading control (Figures 2(a) and 2(b)). The TAp73 isoform, ΔNp73 isoform, and actin western blotting data were quantified using the ImageJ64 program. These values were used to calculate p73 protein N-terminal isoform ratios, in the form of TAp73/ΔNp73, relative to the actin control. Cancer cell line data were consistent with higher levels of TAp73 protein relative to ΔNp73 in the heterozygous cell lines compared to the wild type (Table 3 and Figure 3, P < 0.001). It was noteworthy that the only cancer cell line analyzed that was homozygous polymorphic for the p73 DNP, CaCO-2, contained no detectable p73 protein (Figure 2(b)).

Bottom Line: Methods.Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57-1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45-1.06, P = 0.09).Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Biochemistry & Physics, University of Tampa, Tampa, FL 33606, USA.

ABSTRACT
Background. Molecular markers for prostate cancer (PCa) risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP) in exon 2 of the p73 gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a p73 DNP allele. Methods. We investigated the association between p73 DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls. Results. Although we detected no association between p73 DNP and PCa risk, a significant inverse relationship between p73 DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31-0.99) was detected. Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57-1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45-1.06, P = 0.09). Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (P < 0.001). Conclusions. Our findings are consistent with an association between p73 DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

No MeSH data available.


Related in: MedlinePlus