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

Anchorage-dependent, -independent growth and formation of lung metastases.(A) Growth rates of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 6). (B) Anchorage-independent growth in soft agar of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 4–8). (C) Formation of experimental lung metastases after i.v. injection of 5×105 cells (control, shSep15, shTR1, or shTR1/shSep15) into BALB/c mice (n = 10/construct). (***P<0.001, compared to control).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124487.g002: Anchorage-dependent, -independent growth and formation of lung metastases.(A) Growth rates of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 6). (B) Anchorage-independent growth in soft agar of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 4–8). (C) Formation of experimental lung metastases after i.v. injection of 5×105 cells (control, shSep15, shTR1, or shTR1/shSep15) into BALB/c mice (n = 10/construct). (***P<0.001, compared to control).

Mentions: Anchorage-dependent proliferation of both shSep15 and shTR1 cells was significantly reduced (P<0.001) (Fig 2A). In each case, there were 60% fewer cells on day 4 compared to controls. Surprisingly, the growth pattern of shTR1/shSep15 cells was similar to control cells. shSep15 and shTR1-transfected CT26 cells formed significantly (P<0.001) fewer colonies than control cells in anchorage-independent growth assays (Fig 2B). In contrast, TR1/Sep15 knockdown did not affect colony growth in soft agar.


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)

Anchorage-dependent, -independent growth and formation of lung metastases.(A) Growth rates of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 6). (B) Anchorage-independent growth in soft agar of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 4–8). (C) Formation of experimental lung metastases after i.v. injection of 5×105 cells (control, shSep15, shTR1, or shTR1/shSep15) into BALB/c mice (n = 10/construct). (***P<0.001, compared to control).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124487.g002: Anchorage-dependent, -independent growth and formation of lung metastases.(A) Growth rates of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 6). (B) Anchorage-independent growth in soft agar of shSep15, shTR1 and shTR1/Sep15 cells compared to controls (n = 4–8). (C) Formation of experimental lung metastases after i.v. injection of 5×105 cells (control, shSep15, shTR1, or shTR1/shSep15) into BALB/c mice (n = 10/construct). (***P<0.001, compared to control).
Mentions: Anchorage-dependent proliferation of both shSep15 and shTR1 cells was significantly reduced (P<0.001) (Fig 2A). In each case, there were 60% fewer cells on day 4 compared to controls. Surprisingly, the growth pattern of shTR1/shSep15 cells was similar to control cells. shSep15 and shTR1-transfected CT26 cells formed significantly (P<0.001) fewer colonies than control cells in anchorage-independent growth assays (Fig 2B). In contrast, TR1/Sep15 knockdown did not affect colony growth in soft agar.

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