Limits...
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

Possible connection to Wnt/β-catenin signaling pathway in shTR1/Sep15 cells.mRNA levels of (A) Speg; (B) Ccr1; and (C) Tnc; and (D) Apc in control, shSep15, shTR1, and shTR1/Sep15 cells, as determined by real-time RT-PCR, and expressed relative to Gapdh. Columns, mean (n = 3–6); bars, SE; (**P<0.01, ***P<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4401539&req=5

pone.0124487.g005: Possible connection to Wnt/β-catenin signaling pathway in shTR1/Sep15 cells.mRNA levels of (A) Speg; (B) Ccr1; and (C) Tnc; and (D) Apc in control, shSep15, shTR1, and shTR1/Sep15 cells, as determined by real-time RT-PCR, and expressed relative to Gapdh. Columns, mean (n = 3–6); bars, SE; (**P<0.01, ***P<0.001).

Mentions: In the microarray analyses, genes with significantly altered expression in shTR1 cells compared to controls (S2 Table) included chemokine receptor-type-1 (Ccr1, 9.0-fold), which was also increased in shTR1/shSep15 cells (5.1-fold), and the striated preferentially-expressed-gene (Speg 5.8-fold), which is known to inhibit cell proliferation [26]. Subsequent qPCR analyses showed an about two-fold increase in Speg mRNA expression in shTR1 cells compared to controls (P = 0.09, Fig 5A), and only significant increases in Ccr1 mRNA expression in shTR1/Sep15 cells compared to controls (P<0.001, Fig 5B). The mRNA levels of the cell cycle regulator Ccnb1ip1, which was also previously reported as dramatically increased in shSep15 CT26 cells [18], were also increased in shTR1 cells (P<0.01, Fig 3F). Usp18 mRNA expression, which microarray analyses identified as 16-fold higher (P = 0.09) in shTR1 cells, were also significantly increased (P<0.05) as validated by qPCR (Fig 4C). Significant gene changes in shTR1 cells included those involved in DNA repair, redox regulation, ATP-binding cassette transport, ubiquitination and cancer-related pathways.


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)

Possible connection to Wnt/β-catenin signaling pathway in shTR1/Sep15 cells.mRNA levels of (A) Speg; (B) Ccr1; and (C) Tnc; and (D) Apc in control, shSep15, shTR1, and shTR1/Sep15 cells, as determined by real-time RT-PCR, and expressed relative to Gapdh. Columns, mean (n = 3–6); bars, SE; (**P<0.01, ***P<0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124487.g005: Possible connection to Wnt/β-catenin signaling pathway in shTR1/Sep15 cells.mRNA levels of (A) Speg; (B) Ccr1; and (C) Tnc; and (D) Apc in control, shSep15, shTR1, and shTR1/Sep15 cells, as determined by real-time RT-PCR, and expressed relative to Gapdh. Columns, mean (n = 3–6); bars, SE; (**P<0.01, ***P<0.001).
Mentions: In the microarray analyses, genes with significantly altered expression in shTR1 cells compared to controls (S2 Table) included chemokine receptor-type-1 (Ccr1, 9.0-fold), which was also increased in shTR1/shSep15 cells (5.1-fold), and the striated preferentially-expressed-gene (Speg 5.8-fold), which is known to inhibit cell proliferation [26]. Subsequent qPCR analyses showed an about two-fold increase in Speg mRNA expression in shTR1 cells compared to controls (P = 0.09, Fig 5A), and only significant increases in Ccr1 mRNA expression in shTR1/Sep15 cells compared to controls (P<0.001, Fig 5B). The mRNA levels of the cell cycle regulator Ccnb1ip1, which was also previously reported as dramatically increased in shSep15 CT26 cells [18], were also increased in shTR1 cells (P<0.01, Fig 3F). Usp18 mRNA expression, which microarray analyses identified as 16-fold higher (P = 0.09) in shTR1 cells, were also significantly increased (P<0.05) as validated by qPCR (Fig 4C). Significant gene changes in shTR1 cells included those involved in DNA repair, redox regulation, ATP-binding cassette transport, ubiquitination and cancer-related pathways.

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