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Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis.

Yee NS, Kazi AA, Li Q, Yang Z, Berg A, Yee RK - Biol Open (2015)

Bottom Line: Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors.In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion.The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Program of Experimental Therapeutics, Penn State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA nyee@hmc.psu.edu.

No MeSH data available.


Related in: MedlinePlus

TRPM7 is over-expressed in pancreatic adenocarcinoma cells, and its expression can be down-regulated by shRNA.(A) Cell lysates of each cell line were analyzed for the protein levels of TRPM7 by immunoblotting. The relative amount of TRPM7 and GAPDH protein in each cancer cell line was compared to that in H6c7 as indicated (mean ± standard error). (B) Immunoblotting analysis of TRPM7 protein in BxPC-3 cells transfected with either non-targeting control (NC) shRNA or anti-TRPM7 shRNA. The relative amount of TRPM7 and GAPDH protein in each group of cells is expressed as % of control (NC shRNA). Each column represents the mean ± standard error of three experiments with duplicate samples in each experiment. * indicates statistically significant difference with P<0.05.
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f05: TRPM7 is over-expressed in pancreatic adenocarcinoma cells, and its expression can be down-regulated by shRNA.(A) Cell lysates of each cell line were analyzed for the protein levels of TRPM7 by immunoblotting. The relative amount of TRPM7 and GAPDH protein in each cancer cell line was compared to that in H6c7 as indicated (mean ± standard error). (B) Immunoblotting analysis of TRPM7 protein in BxPC-3 cells transfected with either non-targeting control (NC) shRNA or anti-TRPM7 shRNA. The relative amount of TRPM7 and GAPDH protein in each group of cells is expressed as % of control (NC shRNA). Each column represents the mean ± standard error of three experiments with duplicate samples in each experiment. * indicates statistically significant difference with P<0.05.

Mentions: To further understand the significance of the aberrantly over-expressed TRPM7 in pancreatic cancer, we investigated the role of TRPM7 in cell invasion by reducing its expression. In a previous report, we provided evidence that the levels of TRPM7 mRNA are relatively high in human pancreatic adenocarcinoma cell lines including BxPC-3, PANC-1, MIA PaCa-2, PL45, and Capan-1 (Yee et al., 2011). Moreover, we demonstrated that BxPC-3 and PANC-1 cells with small interfering RNA (siRNA)-mediated repression of TRPM7 exhibited significant reduction of proliferative capability and induction of replicative senescence (Yee et al., 2012b; Yee et al., 2011). Consistent with our previous studies (Yee et al., 2011), the relative level of TRPM7 protein in BxPC-3, PANC-1, and MIA PaCa-2 are relatively high as compared to that in the non-cancerous pancreatic ductal epithelia H6c7 (Fig. 5A). In BxPC-3 cells, anti-TRPM7 short hairpin (shRNA) down-regulated the protein levels of TRPM7 by about 50%, as compared to those transfected with the control non-targeting shRNA (Fig. 5B).


Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis.

Yee NS, Kazi AA, Li Q, Yang Z, Berg A, Yee RK - Biol Open (2015)

TRPM7 is over-expressed in pancreatic adenocarcinoma cells, and its expression can be down-regulated by shRNA.(A) Cell lysates of each cell line were analyzed for the protein levels of TRPM7 by immunoblotting. The relative amount of TRPM7 and GAPDH protein in each cancer cell line was compared to that in H6c7 as indicated (mean ± standard error). (B) Immunoblotting analysis of TRPM7 protein in BxPC-3 cells transfected with either non-targeting control (NC) shRNA or anti-TRPM7 shRNA. The relative amount of TRPM7 and GAPDH protein in each group of cells is expressed as % of control (NC shRNA). Each column represents the mean ± standard error of three experiments with duplicate samples in each experiment. * indicates statistically significant difference with P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4400593&req=5

f05: TRPM7 is over-expressed in pancreatic adenocarcinoma cells, and its expression can be down-regulated by shRNA.(A) Cell lysates of each cell line were analyzed for the protein levels of TRPM7 by immunoblotting. The relative amount of TRPM7 and GAPDH protein in each cancer cell line was compared to that in H6c7 as indicated (mean ± standard error). (B) Immunoblotting analysis of TRPM7 protein in BxPC-3 cells transfected with either non-targeting control (NC) shRNA or anti-TRPM7 shRNA. The relative amount of TRPM7 and GAPDH protein in each group of cells is expressed as % of control (NC shRNA). Each column represents the mean ± standard error of three experiments with duplicate samples in each experiment. * indicates statistically significant difference with P<0.05.
Mentions: To further understand the significance of the aberrantly over-expressed TRPM7 in pancreatic cancer, we investigated the role of TRPM7 in cell invasion by reducing its expression. In a previous report, we provided evidence that the levels of TRPM7 mRNA are relatively high in human pancreatic adenocarcinoma cell lines including BxPC-3, PANC-1, MIA PaCa-2, PL45, and Capan-1 (Yee et al., 2011). Moreover, we demonstrated that BxPC-3 and PANC-1 cells with small interfering RNA (siRNA)-mediated repression of TRPM7 exhibited significant reduction of proliferative capability and induction of replicative senescence (Yee et al., 2012b; Yee et al., 2011). Consistent with our previous studies (Yee et al., 2011), the relative level of TRPM7 protein in BxPC-3, PANC-1, and MIA PaCa-2 are relatively high as compared to that in the non-cancerous pancreatic ductal epithelia H6c7 (Fig. 5A). In BxPC-3 cells, anti-TRPM7 short hairpin (shRNA) down-regulated the protein levels of TRPM7 by about 50%, as compared to those transfected with the control non-targeting shRNA (Fig. 5B).

Bottom Line: Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors.In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion.The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Program of Experimental Therapeutics, Penn State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA nyee@hmc.psu.edu.

No MeSH data available.


Related in: MedlinePlus