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Effect of MUC1/ β -catenin interaction on the tumorigenic capacity of pancreatic CD133 + cells

View Article: PubMed Central - PubMed

ABSTRACT

Despite the fact that the biological function of cluster of differentiation (CD)133 remains unclear, this glycoprotein is currently used in the identification and isolation of tumor-initiating cells from certain malignant tumors, including pancreatic cancer. In the present study, the involvement of mucin 1 (MUC1) in the signaling pathways of a highly tumorigenic CD133+ cellular subpopulation sorted from the pancreatic cancer cell line HPAF-II was evaluated. The expression of MUC1-cytoplasmic domain (MUC1-CD) and oncogenic signaling transducers (epidermal growth factor receptor, protein kinase C delta, glycogen synthase kinase 3 beta and growth factor receptor-bound protein 2), as well as the association between MUC1 and β-catenin, were characterized in HPAF-II CD133+ and CD133low cell subpopulations and in tumor xenografts generated from these cells. Compared with HPAF CD133low cells, HPAF-II CD133+ cancer cells exhibited increased tumorigenic potential in immunocompromised mice, which was associated with overexpression of MUC1 and with the accordingly altered expression profile of MUC1-associated signaling partners. Additionally, MUC1-CD/β-catenin interactions were increased both in the HPAF-II CD133+ cell subpopulation and derived tumor xenografts compared with HPAF CD133low cells. These results suggest that, in comparison with HPAF CD133low cells, CD133+ cells exhibit higher expression of MUC1, which contributes to their tumorigenic phenotype through increased interaction between MUC1-CD and β-catenin, which in turn modulates oncogenic signaling cascades.

No MeSH data available.


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Expression of MUC1 and signaling partners. (A) Expression of MUC1 in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. (B) Expression of MUC1 signaling partners (epidermal growth factor receptor, growth factor receptor-bound protein 2, protein kinase C delta and glycogen synthase kinase 3 beta) in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. MUC1, mucin 1; MUC1-CD, mucin 1 cytoplasmic domain; EGFR, epidermal growth factor receptor; PKCδ, protein kinase C delta; GSK3β, glycogen synthase kinase 3 beta; GRB2, growth factor receptor-bound protein 2; CD, cluster of differentiation; wt, wild-type.
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f2-ol-0-0-4888: Expression of MUC1 and signaling partners. (A) Expression of MUC1 in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. (B) Expression of MUC1 signaling partners (epidermal growth factor receptor, growth factor receptor-bound protein 2, protein kinase C delta and glycogen synthase kinase 3 beta) in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. MUC1, mucin 1; MUC1-CD, mucin 1 cytoplasmic domain; EGFR, epidermal growth factor receptor; PKCδ, protein kinase C delta; GSK3β, glycogen synthase kinase 3 beta; GRB2, growth factor receptor-bound protein 2; CD, cluster of differentiation; wt, wild-type.

Mentions: In order to evaluate the relevance of MUC1 glycoprotein in CD133+ cell biology, the expression levels of MUC1 were analyzed in CD133low and CD133+ subpopulations by immunoblotting (Fig. 2A). HPAF-II CD133+ cells were highly enriched in MUC1 expression, compared with HPAF-II wt and HPAF-II CD133low cells. In addition, MUC1 expression levels in the HPAF-II CD133low cell subpopulation were lower than in HPAF-II wt cells (Fig. 2A).


Effect of MUC1/ β -catenin interaction on the tumorigenic capacity of pancreatic CD133 + cells
Expression of MUC1 and signaling partners. (A) Expression of MUC1 in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. (B) Expression of MUC1 signaling partners (epidermal growth factor receptor, growth factor receptor-bound protein 2, protein kinase C delta and glycogen synthase kinase 3 beta) in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. MUC1, mucin 1; MUC1-CD, mucin 1 cytoplasmic domain; EGFR, epidermal growth factor receptor; PKCδ, protein kinase C delta; GSK3β, glycogen synthase kinase 3 beta; GRB2, growth factor receptor-bound protein 2; CD, cluster of differentiation; wt, wild-type.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998183&req=5

f2-ol-0-0-4888: Expression of MUC1 and signaling partners. (A) Expression of MUC1 in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. (B) Expression of MUC1 signaling partners (epidermal growth factor receptor, growth factor receptor-bound protein 2, protein kinase C delta and glycogen synthase kinase 3 beta) in HPAF-II wt, HPAF-II CD133low and HPAF-II CD133+ cells was evaluated by western blotting. β-actin was used as a loading control. MUC1, mucin 1; MUC1-CD, mucin 1 cytoplasmic domain; EGFR, epidermal growth factor receptor; PKCδ, protein kinase C delta; GSK3β, glycogen synthase kinase 3 beta; GRB2, growth factor receptor-bound protein 2; CD, cluster of differentiation; wt, wild-type.
Mentions: In order to evaluate the relevance of MUC1 glycoprotein in CD133+ cell biology, the expression levels of MUC1 were analyzed in CD133low and CD133+ subpopulations by immunoblotting (Fig. 2A). HPAF-II CD133+ cells were highly enriched in MUC1 expression, compared with HPAF-II wt and HPAF-II CD133low cells. In addition, MUC1 expression levels in the HPAF-II CD133low cell subpopulation were lower than in HPAF-II wt cells (Fig. 2A).

View Article: PubMed Central - PubMed

ABSTRACT

Despite the fact that the biological function of cluster of differentiation (CD)133 remains unclear, this glycoprotein is currently used in the identification and isolation of tumor-initiating cells from certain malignant tumors, including pancreatic cancer. In the present study, the involvement of mucin 1 (MUC1) in the signaling pathways of a highly tumorigenic CD133+ cellular subpopulation sorted from the pancreatic cancer cell line HPAF-II was evaluated. The expression of MUC1-cytoplasmic domain (MUC1-CD) and oncogenic signaling transducers (epidermal growth factor receptor, protein kinase C delta, glycogen synthase kinase 3 beta and growth factor receptor-bound protein 2), as well as the association between MUC1 and β-catenin, were characterized in HPAF-II CD133+ and CD133low cell subpopulations and in tumor xenografts generated from these cells. Compared with HPAF CD133low cells, HPAF-II CD133+ cancer cells exhibited increased tumorigenic potential in immunocompromised mice, which was associated with overexpression of MUC1 and with the accordingly altered expression profile of MUC1-associated signaling partners. Additionally, MUC1-CD/β-catenin interactions were increased both in the HPAF-II CD133+ cell subpopulation and derived tumor xenografts compared with HPAF CD133low cells. These results suggest that, in comparison with HPAF CD133low cells, CD133+ cells exhibit higher expression of MUC1, which contributes to their tumorigenic phenotype through increased interaction between MUC1-CD and β-catenin, which in turn modulates oncogenic signaling cascades.

No MeSH data available.


Related in: MedlinePlus