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Frataxin participates to the hypoxia-induced response in tumors.

Guccini I, Serio D, Condò I, Rufini A, Tomassini B, Mangiola A, Maira G, Anile C, Fina D, Pallone F, Mongiardi MP, Levi A, Ventura N, Testi R, Malisan F - Cell Death Dis (2011)

Bottom Line: Frataxin is a protein required for cell survival since complete knockout is lethal.We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression.Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Biochemical Sciences, Laboratory of Signal Transduction, University Tor Vergata, Rome, Italy.

ABSTRACT
Defective expression of frataxin is responsible for the degenerative disease Friedreich's ataxia. Frataxin is a protein required for cell survival since complete knockout is lethal. Frataxin protects tumor cells against oxidative stress and apoptosis but also acts as a tumor suppressor. The molecular bases of this apparent paradox are missing. We therefore sought to investigate the pathways through which frataxin enhances stress resistance in tumor cells. We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression. Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53. Importantly, we show for the first time that frataxin is in fact increased in human tumors in vivo. These results show that frataxin participates to the hypoxia-induced stress response in tumors, thus implying that modulation of its expression could have a critical role in tumor cell survival and/or progression.

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Related in: MedlinePlus

Frataxin is upregulated in human glioblastoma and colon cancer. Protein extracts (100 μg) were prepared from human glioblastoma and colorectal carcinoma (Tumor) and corresponding normal samples (Healthy). Frataxin expression was analyzed by western blot and normalized with tubulin and β-actin for glioblastoma (a) and colon carcinoma (b), respectively, and frataxin expression in healthy samples set to one. The densitometric quantification of normalized frataxin in the various samples as well as mean upregulation is indicated (mean±1 S.E.M.). Statistical analysis was performed by Student's t-test: *P<0.05; **P<0.01
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fig4: Frataxin is upregulated in human glioblastoma and colon cancer. Protein extracts (100 μg) were prepared from human glioblastoma and colorectal carcinoma (Tumor) and corresponding normal samples (Healthy). Frataxin expression was analyzed by western blot and normalized with tubulin and β-actin for glioblastoma (a) and colon carcinoma (b), respectively, and frataxin expression in healthy samples set to one. The densitometric quantification of normalized frataxin in the various samples as well as mean upregulation is indicated (mean±1 S.E.M.). Statistical analysis was performed by Student's t-test: *P<0.05; **P<0.01

Mentions: To assess whether frataxin levels are modulated in hypoxic tissues in vivo, frataxin was quantitated in human glioblastoma and colon carcinoma tumor samples. Analysis was performed comparing central tumor sample with the adjacent healthy tissue of the same patient. Strikingly, frataxin resulted to be significantly upregulated in >85% of tumor samples analyzed (Figures 4a and b). Frataxin expression was upregulated in 12 out of 14 glioblastoma (Figure 4a), and in 17 out of 20 colorectal carcinoma tumor samples (Figure 4b), compared with the adjacent healthy tissue. The average frataxin upregulation resulted in 2.50- and 1.42-fold increase in glioblastoma and colorectal carcinoma tumors, respectively, and was statistically significant both in glioblastomas and colorectal carcinomas (P<0.01).


Frataxin participates to the hypoxia-induced response in tumors.

Guccini I, Serio D, Condò I, Rufini A, Tomassini B, Mangiola A, Maira G, Anile C, Fina D, Pallone F, Mongiardi MP, Levi A, Ventura N, Testi R, Malisan F - Cell Death Dis (2011)

Frataxin is upregulated in human glioblastoma and colon cancer. Protein extracts (100 μg) were prepared from human glioblastoma and colorectal carcinoma (Tumor) and corresponding normal samples (Healthy). Frataxin expression was analyzed by western blot and normalized with tubulin and β-actin for glioblastoma (a) and colon carcinoma (b), respectively, and frataxin expression in healthy samples set to one. The densitometric quantification of normalized frataxin in the various samples as well as mean upregulation is indicated (mean±1 S.E.M.). Statistical analysis was performed by Student's t-test: *P<0.05; **P<0.01
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101705&req=5

fig4: Frataxin is upregulated in human glioblastoma and colon cancer. Protein extracts (100 μg) were prepared from human glioblastoma and colorectal carcinoma (Tumor) and corresponding normal samples (Healthy). Frataxin expression was analyzed by western blot and normalized with tubulin and β-actin for glioblastoma (a) and colon carcinoma (b), respectively, and frataxin expression in healthy samples set to one. The densitometric quantification of normalized frataxin in the various samples as well as mean upregulation is indicated (mean±1 S.E.M.). Statistical analysis was performed by Student's t-test: *P<0.05; **P<0.01
Mentions: To assess whether frataxin levels are modulated in hypoxic tissues in vivo, frataxin was quantitated in human glioblastoma and colon carcinoma tumor samples. Analysis was performed comparing central tumor sample with the adjacent healthy tissue of the same patient. Strikingly, frataxin resulted to be significantly upregulated in >85% of tumor samples analyzed (Figures 4a and b). Frataxin expression was upregulated in 12 out of 14 glioblastoma (Figure 4a), and in 17 out of 20 colorectal carcinoma tumor samples (Figure 4b), compared with the adjacent healthy tissue. The average frataxin upregulation resulted in 2.50- and 1.42-fold increase in glioblastoma and colorectal carcinoma tumors, respectively, and was statistically significant both in glioblastomas and colorectal carcinomas (P<0.01).

Bottom Line: Frataxin is a protein required for cell survival since complete knockout is lethal.We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression.Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Biochemical Sciences, Laboratory of Signal Transduction, University Tor Vergata, Rome, Italy.

ABSTRACT
Defective expression of frataxin is responsible for the degenerative disease Friedreich's ataxia. Frataxin is a protein required for cell survival since complete knockout is lethal. Frataxin protects tumor cells against oxidative stress and apoptosis but also acts as a tumor suppressor. The molecular bases of this apparent paradox are missing. We therefore sought to investigate the pathways through which frataxin enhances stress resistance in tumor cells. We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression. Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53. Importantly, we show for the first time that frataxin is in fact increased in human tumors in vivo. These results show that frataxin participates to the hypoxia-induced stress response in tumors, thus implying that modulation of its expression could have a critical role in tumor cell survival and/or progression.

Show MeSH
Related in: MedlinePlus