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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

Cell cycle analysis.Percent of cells in each cell cycle phase as determined by FACS analysis at (A) 0 h; (B) 6 h; (C) 24 h; and (D) 48 h after release from cell synchronization. mRNA expression of (E) CyclinB1 (Ccnb1), and (F) CyclinB1 Interacting-Protein-1 (Ccnb1ip1), as determined by real-time RT-PCR. Columns, mean (n = 3–9); bars, SE; (*P<0.05, **P<0.01, ***P<0.001).
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pone.0124487.g003: Cell cycle analysis.Percent of cells in each cell cycle phase as determined by FACS analysis at (A) 0 h; (B) 6 h; (C) 24 h; and (D) 48 h after release from cell synchronization. mRNA expression of (E) CyclinB1 (Ccnb1), and (F) CyclinB1 Interacting-Protein-1 (Ccnb1ip1), as determined by real-time RT-PCR. Columns, mean (n = 3–9); bars, SE; (*P<0.05, **P<0.01, ***P<0.001).

Mentions: The most striking cell cycle changes were observed in shSep15 cells (Fig 3A–3D), and agree with our previously published observations, that the most significant differences between shSep15 and control cells appeared around 24 h past release from serum starvation [18]. shSep15 cells had a substantially higher percentage of their population in the G2/M-phase (27.8±0.8%) than control cells (11.5±2.1%; P<0.001), and a smaller percentage in S-phase (25.1±0.9% versus 42.3±1.9%), similar to earlier observations [18]. However, shTR1 and shTR1/shSep15 cells had fewer cells in G2/M-phase (15.6±1.2% and 17.7±0.7%, respectively) compared to shSep15 cells (P<0.001). shTR1 cells, as observed in fibroblast-derived DT cells previously [15], manifested defective progression in S-phase, visible as an increased percentage of the cell population at 6 and 48 h. CyclinB1 (Ccnb1) mRNA levels did not significantly differ (Fig 3E), but the mRNA levels of CyclinB1-interacting-protein-1 (Ccnbip1) were strongly elevated in shTR1 and shSep15 cells (P<0.01), but not in shTR1/shSep15 cells, compared to controls, respectively (Fig 3F).


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)

Cell cycle analysis.Percent of cells in each cell cycle phase as determined by FACS analysis at (A) 0 h; (B) 6 h; (C) 24 h; and (D) 48 h after release from cell synchronization. mRNA expression of (E) CyclinB1 (Ccnb1), and (F) CyclinB1 Interacting-Protein-1 (Ccnb1ip1), as determined by real-time RT-PCR. Columns, mean (n = 3–9); bars, SE; (*P<0.05, **P<0.01, ***P<0.001).
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Related In: Results  -  Collection

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

pone.0124487.g003: Cell cycle analysis.Percent of cells in each cell cycle phase as determined by FACS analysis at (A) 0 h; (B) 6 h; (C) 24 h; and (D) 48 h after release from cell synchronization. mRNA expression of (E) CyclinB1 (Ccnb1), and (F) CyclinB1 Interacting-Protein-1 (Ccnb1ip1), as determined by real-time RT-PCR. Columns, mean (n = 3–9); bars, SE; (*P<0.05, **P<0.01, ***P<0.001).
Mentions: The most striking cell cycle changes were observed in shSep15 cells (Fig 3A–3D), and agree with our previously published observations, that the most significant differences between shSep15 and control cells appeared around 24 h past release from serum starvation [18]. shSep15 cells had a substantially higher percentage of their population in the G2/M-phase (27.8±0.8%) than control cells (11.5±2.1%; P<0.001), and a smaller percentage in S-phase (25.1±0.9% versus 42.3±1.9%), similar to earlier observations [18]. However, shTR1 and shTR1/shSep15 cells had fewer cells in G2/M-phase (15.6±1.2% and 17.7±0.7%, respectively) compared to shSep15 cells (P<0.001). shTR1 cells, as observed in fibroblast-derived DT cells previously [15], manifested defective progression in S-phase, visible as an increased percentage of the cell population at 6 and 48 h. CyclinB1 (Ccnb1) mRNA levels did not significantly differ (Fig 3E), but the mRNA levels of CyclinB1-interacting-protein-1 (Ccnbip1) were strongly elevated in shTR1 and shSep15 cells (P<0.01), but not in shTR1/shSep15 cells, compared to controls, respectively (Fig 3F).

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