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

Randhawa H, Chikara S, Gehring D, Yildirim T, Menon J, Reindl KM - BMC Cancer (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, North Dakota State University, Fargo, ND, USA.

ABSTRACT

Background: Human 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.

Methods: The 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.

Results: PDF 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.

Conclusions: This 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.

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Related in: MedlinePlus

PDF and MAP1D mRNA expression varies with stage in breast, colon, and lung cancer samples. (A) PDF and (B) MAP1D mRNA expression is shown for normal (●) tissues relative to stage I (○), stage II (▼), and stage III (Δ) tissues for breast, colon, and lung cancer patients. PDF levels are significantly (*) elevated in late-stage breast, and early-stage colon and lung cancers while MAP1D levels are significantly increased in early-stage colon cancer, but decreased in breast cancer.
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Figure 4: PDF and MAP1D mRNA expression varies with stage in breast, colon, and lung cancer samples. (A) PDF and (B) MAP1D mRNA expression is shown for normal (●) tissues relative to stage I (○), stage II (▼), and stage III (Δ) tissues for breast, colon, and lung cancer patients. PDF levels are significantly (*) elevated in late-stage breast, and early-stage colon and lung cancers while MAP1D levels are significantly increased in early-stage colon cancer, but decreased in breast cancer.

Mentions: Additional tissue panels for breast, colon, and lung cancer patients were used to validate the previous results and to assess MAP1D levels in these cancer types. Colon and lung tissue panels contained 48 matched normal and cancer tissue samples from 24 cancer patients while the breast tissue panels contained 48 unmatched tissue samples that included 12 normal breast tissue controls and 36 breast cancer samples at various disease stages. Similar to the first results, PDF was elevated in breast, colon, and lung cancer samples and showed stage-dependent expression with the highest expression in late stage breast cancer, but early stage colon and lung cancers (Figure 4A). MAP1D mRNA expression was elevated in early-stage colon cancer samples, and was surprisingly reduced in breast cancer samples compared to control samples (Figure 4B). There was no significant change in MAP1D mRNA levels in lung cancer samples at any stage compared to control. These results suggest PDF and MAP1D expression is altered in certain cancer tissues and that expression of these enzymes is correlated with the stage of disease.


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

Randhawa H, Chikara S, Gehring D, Yildirim T, Menon J, Reindl KM - BMC Cancer (2013)

PDF and MAP1D mRNA expression varies with stage in breast, colon, and lung cancer samples. (A) PDF and (B) MAP1D mRNA expression is shown for normal (●) tissues relative to stage I (○), stage II (▼), and stage III (Δ) tissues for breast, colon, and lung cancer patients. PDF levels are significantly (*) elevated in late-stage breast, and early-stage colon and lung cancers while MAP1D levels are significantly increased in early-stage colon cancer, but decreased in breast cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3722014&req=5

Figure 4: PDF and MAP1D mRNA expression varies with stage in breast, colon, and lung cancer samples. (A) PDF and (B) MAP1D mRNA expression is shown for normal (●) tissues relative to stage I (○), stage II (▼), and stage III (Δ) tissues for breast, colon, and lung cancer patients. PDF levels are significantly (*) elevated in late-stage breast, and early-stage colon and lung cancers while MAP1D levels are significantly increased in early-stage colon cancer, but decreased in breast cancer.
Mentions: Additional tissue panels for breast, colon, and lung cancer patients were used to validate the previous results and to assess MAP1D levels in these cancer types. Colon and lung tissue panels contained 48 matched normal and cancer tissue samples from 24 cancer patients while the breast tissue panels contained 48 unmatched tissue samples that included 12 normal breast tissue controls and 36 breast cancer samples at various disease stages. Similar to the first results, PDF was elevated in breast, colon, and lung cancer samples and showed stage-dependent expression with the highest expression in late stage breast cancer, but early stage colon and lung cancers (Figure 4A). MAP1D mRNA expression was elevated in early-stage colon cancer samples, and was surprisingly reduced in breast cancer samples compared to control samples (Figure 4B). There was no significant change in MAP1D mRNA levels in lung cancer samples at any stage compared to control. These results suggest PDF and MAP1D expression is altered in certain cancer tissues and that expression of these enzymes is correlated with the stage of disease.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, North Dakota State University, Fargo, ND, USA.

ABSTRACT

Background: Human 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.

Methods: The 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.

Results: PDF 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.

Conclusions: This 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.

Show MeSH
Related in: MedlinePlus