Overexpression of peptide deformylase in breast, colon, and lung cancers

Abstract

BackgroundHuman mitochondrial peptide deformylase (PDF) has been proposed as a novel cancer therapeutic target. However, very little is known about its expression and regulation in human tissues. The purpose of this study was to characterize the expression pattern of PDF in cancerous tissues and to identify mechanisms that regulate its expression.MethodsThe mRNA expression levels of PDF and methionine aminopeptidase 1D (MAP1D), an enzyme involved in a related pathway with PDF, were determined using tissue panels containing cDNA from patients with various types of cancer (breast, colon, kidney, liver, lung, ovarian, prostate, or thyroid) and human cell lines. Protein levels of PDF were also determined in 2 colon cancer patients via western blotting. Colon cancer cells were treated with inhibitors of ERK, Akt, and mTOR signaling pathways and the resulting effects on PDF and MAP1D mRNA levels were determined by qPCR for colon and lung cancer cell lines. Finally, the effects of a PDF inhibitor, actinonin, on the proliferation of breast, colon, and prostate cell lines were determined using the CyQUANT assay.ResultsPDF and MAP1D mRNA levels were elevated in cancer cell lines compared to non-cancer lines. PDF mRNA levels were significantly increased in breast, colon, and lung cancer samples while MAP1D mRNA levels were increased in just colon cancers. The expression of PDF and MAP1D varied with stage in these cancers. Further, PDF protein expression was elevated in colon cancer tissue samples. Inhibition of the MEK/ERK, but not PI3K or mTOR, pathway reduced the expression of PDF and MAP1D in both colon and lung cancer cell lines. Further, inhibition of PDF with actinonin resulted in greater reduction of breast, colon, and prostate cancer cell proliferation than non-cancer cell lines.ConclusionsThis is the first report showing that PDF is over-expressed in breast, colon, and lung cancers, and the first evidence that the MEK/ERK pathway plays a role in regulating the expression of PDF and MAP1D. The over-expression of PDF in several cancers and the inhibition of cancer cell growth by a PDF inhibitor suggest this enzyme may act as an oncogene to promote cancer cell proliferation.

Patterns of differentially expressed genes in oral mucosal lesions visualised under autofluorescence (VELscope™)

“…Unfortunately, the causes for blanching within the lichenoid cohort could not be elucidated from the data provided although GO analysis revealed SERPINE3, a gene of the Serpin family known to have roles in inflammation, immune function, angiogenesis and tumorigenesis (Heit et al , ). This was accompanied with the overexpression of PDF (peptide deformylase), an oncogene which has been involved in cell proliferation in colon, lung and breast cancers (Randhawa et al , ), but its role in oral tumorigenesis is currently unknown.…”

Metabolomics method to comprehensively analyze amino acids in different domains

“…17, 28, 36, 37 Carcinogenesis of CRC is a complex process involving multiple genetic abnormalities such as mutations in both tumor suppressor genes and oncogenic mediators. 38–41 An important consequence of this complex progression could be the altered uptake and usage of amino acids, which have been recognized in metabolomics as putative markers for diagnosing colon cancer.…”

Peptide deformylase inhibitor actinonin reduces celastrol’s HSP70 induction while synergizing proliferation inhibition in tumor cells

“…Since actinonin itself is an anti-tumor agent [30], its combinative use with celastrol in anti-tumor applications is suggested here.…”