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The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.

Tsuji PA, Carlson BA, Yoo MH, Naranjo-Suarez S, Xu XM, He Y, Asaki E, Seifried HE, Reinhold WC, Davis CD, Gladyshev VN, Hatfield DL - PLoS ONE (2015)

Bottom Line: We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells.These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells.Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Towson University, Towson, Maryland, United States of America.

ABSTRACT
Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

No MeSH data available.


Related in: MedlinePlus

Signatures of selected NCI-60 cell lines for Sep15 and Stat-1.Opposing directions of transcript intensity scores (z-scores) for Sep15 and Stat-1 mRNAs were highly significant (r = -0.646, P<0.01) for human central nervous system (CNS), leukemia and ovarian cancer cell lines. Mean centered average protein activity patterns for Stat-1 (Stat-1_20 antibody) significantly correlated (r = 0.661, P<0.01) with Stat-1 mRNA expression.
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pone.0124487.g006: Signatures of selected NCI-60 cell lines for Sep15 and Stat-1.Opposing directions of transcript intensity scores (z-scores) for Sep15 and Stat-1 mRNAs were highly significant (r = -0.646, P<0.01) for human central nervous system (CNS), leukemia and ovarian cancer cell lines. Mean centered average protein activity patterns for Stat-1 (Stat-1_20 antibody) significantly correlated (r = 0.661, P<0.01) with Stat-1 mRNA expression.

Mentions: In the NCI-60 cell lines, CellMiner negatively correlated (P<0.05) mRNA expression of Sep15, but not TR1, with Stat-2 (Pearson’s coefficient: -0.29) and with Usp18 (Pearson’s coefficient: −0.43), the second highest up-regulated gene signal in cells lacking Sep15. Comparison of cell line signatures revealed that the opposing directions of mRNA transcript intensity scores (z-scores) for Sep15 and Stat-1 (Fig 6) were particularly significant (r = −0.65, P<0.01) for human cancer cell lines derived from central nervous system, leukemia and ovarian cancers. Stat-1 protein levels in NCI-60 cell lines supported the negative correlation with Sep15 mRNA expression (Fig 6).


The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.

Tsuji PA, Carlson BA, Yoo MH, Naranjo-Suarez S, Xu XM, He Y, Asaki E, Seifried HE, Reinhold WC, Davis CD, Gladyshev VN, Hatfield DL - PLoS ONE (2015)

Signatures of selected NCI-60 cell lines for Sep15 and Stat-1.Opposing directions of transcript intensity scores (z-scores) for Sep15 and Stat-1 mRNAs were highly significant (r = -0.646, P<0.01) for human central nervous system (CNS), leukemia and ovarian cancer cell lines. Mean centered average protein activity patterns for Stat-1 (Stat-1_20 antibody) significantly correlated (r = 0.661, P<0.01) with Stat-1 mRNA expression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401539&req=5

pone.0124487.g006: Signatures of selected NCI-60 cell lines for Sep15 and Stat-1.Opposing directions of transcript intensity scores (z-scores) for Sep15 and Stat-1 mRNAs were highly significant (r = -0.646, P<0.01) for human central nervous system (CNS), leukemia and ovarian cancer cell lines. Mean centered average protein activity patterns for Stat-1 (Stat-1_20 antibody) significantly correlated (r = 0.661, P<0.01) with Stat-1 mRNA expression.
Mentions: In the NCI-60 cell lines, CellMiner negatively correlated (P<0.05) mRNA expression of Sep15, but not TR1, with Stat-2 (Pearson’s coefficient: -0.29) and with Usp18 (Pearson’s coefficient: −0.43), the second highest up-regulated gene signal in cells lacking Sep15. Comparison of cell line signatures revealed that the opposing directions of mRNA transcript intensity scores (z-scores) for Sep15 and Stat-1 (Fig 6) were particularly significant (r = −0.65, P<0.01) for human cancer cell lines derived from central nervous system, leukemia and ovarian cancers. Stat-1 protein levels in NCI-60 cell lines supported the negative correlation with Sep15 mRNA expression (Fig 6).

Bottom Line: We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells.These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells.Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Towson University, Towson, Maryland, United States of America.

ABSTRACT
Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

No MeSH data available.


Related in: MedlinePlus