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Cisplatin fails to induce puma mediated apoptosis in mucosal melanomas.

Fritsche MK, Metzler V, Becker K, Plettenberg C, Heiser C, Hofauer B, Knopf A - Oncotarget (2015)

Bottom Line: IHC and WB confirmed high p53 expression in all melanomas.Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004).WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM.

View Article: PubMed Central - PubMed

Affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.

ABSTRACT

Objectives: Mucosal melanomas (MM) are aggressive subtypes of common melanomas. It remains unclear whether limitations in their resectability or their distinctive molecular mechanisms are responsible for the aggressive phenotype.

Methods: In total, 112 patients with cutaneous melanomas (CM) and 27 patients with MM were included. Clinical parameters were analysed using Chi square, Fisher exact and student's t-test. Survival rates were calculated by Kaplan-Meier. Analysis of p53, p21, Mdm2, Hipk2, Gadd45, Puma, Bax, Casp9 and Cdk1 via quantitative PCR and immunohistochemistry (IHC) was performed. TP53 induction after cisplatin treatment was analysed in 10 cell lines (melanocytes, four MM and five CM) using western blot (WB) and qPCR.

Results: The overall/recurrence-free survival differed significantly between MM (40 months and 30 months) and CM (90 months and 107 months; p < 0.001). IHC and WB confirmed high p53 expression in all melanomas. Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004). QPCR and WB of wild-type cell lines demonstrated no differences for p53, p21, Mdm2, Bax and Casp9. WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM.

Conclusions: The aggressive phenotype of MM did not appear to be due to differential expressions of p53, p21, Mdm2, Bax or Casp9. A non-functional apoptosis in MM may have further clinical implications.

No MeSH data available.


Related in: MedlinePlus

Quantitative PCR of the p53 pathway in FFPE tumor samplesResults were normalized to GAPDH and shown as fold induction compared to CM. MM: Mucosal melanoma; CM Cutaneous melanoma.
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Figure 2: Quantitative PCR of the p53 pathway in FFPE tumor samplesResults were normalized to GAPDH and shown as fold induction compared to CM. MM: Mucosal melanoma; CM Cutaneous melanoma.

Mentions: QPCR of FFPE tumour samples did not show significant differences in the expression of TP53, BBC3, CASP9, BCL2A1, and CDK1. HIPK2, MDM2, CDKN1A, and BAX mRNA expression was increased in MuM demonstrating differences from 2.6- to 4.2-fold. GADD45 showed 2.4-fold decreased expression in MM (Figure 2).


Cisplatin fails to induce puma mediated apoptosis in mucosal melanomas.

Fritsche MK, Metzler V, Becker K, Plettenberg C, Heiser C, Hofauer B, Knopf A - Oncotarget (2015)

Quantitative PCR of the p53 pathway in FFPE tumor samplesResults were normalized to GAPDH and shown as fold induction compared to CM. MM: Mucosal melanoma; CM Cutaneous melanoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496404&req=5

Figure 2: Quantitative PCR of the p53 pathway in FFPE tumor samplesResults were normalized to GAPDH and shown as fold induction compared to CM. MM: Mucosal melanoma; CM Cutaneous melanoma.
Mentions: QPCR of FFPE tumour samples did not show significant differences in the expression of TP53, BBC3, CASP9, BCL2A1, and CDK1. HIPK2, MDM2, CDKN1A, and BAX mRNA expression was increased in MuM demonstrating differences from 2.6- to 4.2-fold. GADD45 showed 2.4-fold decreased expression in MM (Figure 2).

Bottom Line: IHC and WB confirmed high p53 expression in all melanomas.Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004).WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM.

View Article: PubMed Central - PubMed

Affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.

ABSTRACT

Objectives: Mucosal melanomas (MM) are aggressive subtypes of common melanomas. It remains unclear whether limitations in their resectability or their distinctive molecular mechanisms are responsible for the aggressive phenotype.

Methods: In total, 112 patients with cutaneous melanomas (CM) and 27 patients with MM were included. Clinical parameters were analysed using Chi square, Fisher exact and student's t-test. Survival rates were calculated by Kaplan-Meier. Analysis of p53, p21, Mdm2, Hipk2, Gadd45, Puma, Bax, Casp9 and Cdk1 via quantitative PCR and immunohistochemistry (IHC) was performed. TP53 induction after cisplatin treatment was analysed in 10 cell lines (melanocytes, four MM and five CM) using western blot (WB) and qPCR.

Results: The overall/recurrence-free survival differed significantly between MM (40 months and 30 months) and CM (90 months and 107 months; p < 0.001). IHC and WB confirmed high p53 expression in all melanomas. Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004). QPCR and WB of wild-type cell lines demonstrated no differences for p53, p21, Mdm2, Bax and Casp9. WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM.

Conclusions: The aggressive phenotype of MM did not appear to be due to differential expressions of p53, p21, Mdm2, Bax or Casp9. A non-functional apoptosis in MM may have further clinical implications.

No MeSH data available.


Related in: MedlinePlus