|
|
char = T;code = 84
char = G;code = 71
char = F;code = 70
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char = ;code = 32
char = P;code = 80
char = T;code = 84
char = E;code = 69
char = N;code = 78
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char = s;code = 115
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char = p;code = 112
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char = s;code = 115
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char = l;code = 108
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char = t;code = 116
char = y;code = 121
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char = o;code = 111
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char = h;code = 104
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char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = P;code = 80
char = K;code = 75
char = C;code = 67
char = -;code = 45
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = c;code = 99
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char = v;code = 118
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char = t;code = 116
char = i;code = 105
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char = i;code = 105
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
result sql = TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKC-alpha activation in pancreatic cancer cells.
TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKC-alpha activation in pancreatic cancer cells.char = T;code = 84
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char = g;code = 103
char = r;code = 114
char = o;code = 111
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char = t;code = 116
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char = a;code = 97
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char = t;code = 116
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char = -;code = 45
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char = a;code = 97
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char = (;code = 40
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char = p;code = 112
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char = s;code = 115
char = e;code = 101
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char = d;code = 100
char = ;code = 32
char = S;code = 83
char = M;code = 77
char = A;code = 65
char = D;code = 68
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = a;code = 97
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char = .;code = 46
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char = T;code = 84
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char = .;code = 46
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char = H;code = 72
char = e;code = 101
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result sql = Transforming growth factor-beta (TGF-beta) suppresses growth via the TGF-beta-SMAD pathway but promotes growth in cancer cells with disrupted SMAD signaling and corresponds to an invasive phenotype. TGF-beta also downregulates the tumor suppressor PTEN that is rarely mutated in sporadic pancreatic cancer; this downregulation may mediate cell proliferation and invasiveness, but the mechanism is unknown. Here, we examined whether TGF-beta modulation of PTEN was mediated by protein kinase C (PKC). We have previously demonstrated that SMAD4-null BxPc-3 pancreatic cancer cells treated with TGF-beta1 (10 ng/ml) suppressed PTEN expression and increased cell proliferation. TGF-beta-treated cells were examined for PKC activation and its coupling to PTEN expression, utilizing pharmacological and knockdown methods. Calcium mobilization and cell migration were also examined. In BxPc-3 cells, only two PKC isoforms were activated by TGF-beta, and PTEN downregulation by TGF-beta was specifically mediated by PKC-alpha. In parallel, TGF-beta rapidly induced an increase in cytoplasmic free calcium from intracellular stores, consistent with subsequent PKC-alpha activation. The TGF-beta-induced increase in cell migration was blocked by knockdown of PKC-alpha. Thus calcium-dependent PKC-alpha mediates TGF-beta-induced transcriptional downregulation of PTEN, and this pathway promotes cell migration in a SMAD4-null environment. The TGF-beta-PKC-alpha-PTEN cascade may be a key pathway for pancreatic cancer cells to proliferate and metastasize.
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result sql = TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKC-alpha activation in pancreatic cancer cells.
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result sql = Transforming growth factor-beta (TGF-beta) suppresses growth via the TGF-beta-SMAD pathway but promotes growth in cancer cells with disrupted SMAD signaling and corresponds to an invasive phenotype. TGF-beta also downregulates the tumor suppressor PTEN that is rarely mutated in sporadic pancreatic cancer; this downregulation may mediate cell proliferation and invasiveness, but the mechanism is unknown. Here, we examined whether TGF-beta modulation of PTEN was mediated by protein kinase C (PKC). We have previously demonstrated that SMAD4-null BxPc-3 pancreatic cancer cells treated with TGF-beta1 (10 ng/ml) suppressed PTEN expression and increased cell proliferation. TGF-beta-treated cells were examined for PKC activation and its coupling to PTEN expression, utilizing pharmacological and knockdown methods. Calcium mobilization and cell migration were also examined. In BxPc-3 cells, only two PKC isoforms were activated by TGF-beta, and PTEN downregulation by TGF-beta was specifically mediated by PKC-alpha. In parallel, TGF-beta rapidly induced an increase in cytoplasmic free calcium from intracellular stores, consistent with subsequent PKC-alpha activation. The TGF-beta-induced increase in cell migration was blocked by knockdown of PKC-alpha. Thus calcium-dependent PKC-alpha mediates TGF-beta-induced transcriptional downregulation of PTEN, and this pathway promotes cell migration in a SMAD4-null environment. The TGF-beta-PKC-alpha-PTEN cascade may be a key pathway for pancreatic cancer cells to proliferate and metastasize.
Publication: Am. J. Physiol. Gastrointest. Liver Physiol. 2008 Apr ;294(4)::G899-905. :doi: 10.1152/ajpgi.00411.2007.
Publication Date: 2008 Apr
Study Author(s): Chow, Jimmy Y C;Dong, Hui;Quach, Khai T;Van Nguyen, Phuoc Nam;Chen, Kevin;Carethers, John M;
Institution: Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, California, USA.
Shortcut link to this study:
Publication Date: 2008 Apr
Study Author(s): Chow, Jimmy Y C;Dong, Hui;Quach, Khai T;Van Nguyen, Phuoc Nam;Chen, Kevin;Carethers, John M;
Institution: Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, California, USA.
Shortcut link to this study:
Transforming growth factor-beta (TGF-beta) suppresses growth via the TGF-beta-SMAD pathway but promotes growth in cancer cells with disrupted SMAD signaling and corresponds to an invasive phenotype. TGF-beta also downregulates the tumor suppressor PTEN that is rarely mutated in sporadic pancreatic cancer; this downregulation may mediate cell proliferation and invasiveness, but the mechanism is unknown. Here, we examined whether TGF-beta modulation of PTEN was mediated by protein kinase C (PKC). We have previously demonstrated that SMAD4-null BxPc-3 pancreatic cancer cells treated with TGF-beta1 (10 ng/ml) suppressed PTEN expression and increased cell proliferation. TGF-beta-treated cells were examined for PKC activation and its coupling to PTEN expression, utilizing pharmacological and knockdown methods. Calcium mobilization and cell migration were also examined. In BxPc-3 cells, only two PKC isoforms were activated by TGF-beta, and PTEN downregulation by TGF-beta was specifically mediated by PKC-alpha. In parallel, TGF-beta rapidly induced an increase in cytoplasmic free calcium from intracellular stores, consistent with subsequent PKC-alpha activation. The TGF-beta-induced increase in cell migration was blocked by knockdown of PKC-alpha. Thus calcium-dependent PKC-alpha mediates TGF-beta-induced transcriptional downregulation of PTEN, and this pathway promotes cell migration in a SMAD4-null environment. The TGF-beta-PKC-alpha-PTEN cascade may be a key pathway for pancreatic cancer cells to proliferate and metastasize.
PMID: 18239055
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