Methionine aminopeptidase-2 regulates human mesothelioma cell survival: Role of Bcl-2 expression and telomerase activity

A. Catalano, M. Romano, I. Robuffo, L. Strizzi, A. Procopio

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Abstract

Methionine aminopeptidase-2 (MetAP2) is the molecular target of the angiogenesis inhibitors, fumagillin and ovalacin. Fumagillin can also inhibit cancer cell proliferation, implying that MetAP2 may play a quite complex role in tumor progression. Here, we examined the expression and function of MetAP2 in an in vitro model of human mesothelioma. We found that mesothelioma cells expressed higher MetAP2 mRNA levels than primary normal mesothelial cells. Consistently, fumagillin induced apoptosis, owing to early mitochondrial damage, in malignant, but not in normal mesothelial cells. Transfection of mesothelioma cells with a MetAP2 anti-sense oligonucleotide determined a time-dependent inhibition of cell survival and induced nucleosome formation. Interestingly, mRNA and protein levels of the anti-apoptotic gene bcl-2 as well as telomerase activity were selectively reduced after MetAP2 inhibition in mesothelioma cells, whereas bcl-2 overexpression counteracted the effect of MetAP2 inhibition on telomerase activity and apoptosis. MetAP2 inhibition also increased caspase activity and the caspase inhibitor, zVAD-fmk, prevented fumagillin-induced apoptosis, but it did not alter telomerase activity. These results indicate that MetAP2 is a main regulator of proliferative and apoptotic pathways in mesothelioma cells and suggest that MetAP2 inhibition may represent a potential target for therapeutic intervention in human mesothelioma.

Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalAmerican Journal of Pathology
Volume159
Issue number2
Publication statusPublished - 2001

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Telomerase
Mesothelioma
Cell Survival
Apoptosis
methionine aminopeptidase 2
bcl-2 Genes
Messenger RNA
Apoptosis Regulatory Proteins
Caspase Inhibitors
Angiogenesis Inhibitors
Nucleosomes
Antisense Oligonucleotides
Caspases
Transfection
Neoplasms
Cell Proliferation
fumagillin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Methionine aminopeptidase-2 regulates human mesothelioma cell survival : Role of Bcl-2 expression and telomerase activity. / Catalano, A.; Romano, M.; Robuffo, I.; Strizzi, L.; Procopio, A.

In: American Journal of Pathology, Vol. 159, No. 2, 2001, p. 721-731.

Research output: Contribution to journalArticle

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