Akt and phospholipase Cγ are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin
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Akt and phospholipase Cγ are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin. / Tomas, Nicola M; Masur, Kai; Piecha, Jonas C; Niggemann, Bernd; Zänker, Kurt S.
in: BMC RES NOTES, Jahrgang 5, 214, 10.07.2012.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › Kurzpublikation › Forschung › Begutachtung
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TY - JOUR
T1 - Akt and phospholipase Cγ are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin
AU - Tomas, Nicola M
AU - Masur, Kai
AU - Piecha, Jonas C
AU - Niggemann, Bernd
AU - Zänker, Kurt S
PY - 2012/7/10
Y1 - 2012/7/10
N2 - BACKGROUND: Epidemiological studies revealed a strong correlation between the metabolic syndrome/diabetes mellitus type 2 (DM2) and higher incidence and faster progression of breast and colon cancer. However, the underlying molecular mechanisms are widely unknown. Akt and phospholipase Cγ (PLCγ) are involved in tyrosine kinase signaling and promote tumor cell growth and migration. Therefore, we examined regulatory functions and expression of Akt and PLCγ in a simplified in vitro diabetogenic model.FINDINGS: Protein expression was determined by western blot analysis in MDA-MB-468 breast cancer and SW480 colon cancer cells previously cultured under physiologic (5.5 mM) and diabetogenic (11 mM) glucose concentrations (without and with 100 ng/ml insulin). We studied the culture effects on proliferation and migration of these cells, especially after inhibiting Akt and PLCγ. We found that Akt expression was up-regulated with high glucose and insulin in both cell lines, whereas PLCγ expression was enhanced in colon cancer cells only. High levels of glucose and insulin increased cell proliferation and migration in both cell lines in vitro, mediated by Akt and PLCγ, as shown through the specific pharmacological inhibitors A6730 and U73122.CONCLUSIONS: Our molecular data explain glucose- and insulin-induced changes in a cancer cell and help to understand what might trigger tumor cell proliferation and migration in DM2 patients, too.
AB - BACKGROUND: Epidemiological studies revealed a strong correlation between the metabolic syndrome/diabetes mellitus type 2 (DM2) and higher incidence and faster progression of breast and colon cancer. However, the underlying molecular mechanisms are widely unknown. Akt and phospholipase Cγ (PLCγ) are involved in tyrosine kinase signaling and promote tumor cell growth and migration. Therefore, we examined regulatory functions and expression of Akt and PLCγ in a simplified in vitro diabetogenic model.FINDINGS: Protein expression was determined by western blot analysis in MDA-MB-468 breast cancer and SW480 colon cancer cells previously cultured under physiologic (5.5 mM) and diabetogenic (11 mM) glucose concentrations (without and with 100 ng/ml insulin). We studied the culture effects on proliferation and migration of these cells, especially after inhibiting Akt and PLCγ. We found that Akt expression was up-regulated with high glucose and insulin in both cell lines, whereas PLCγ expression was enhanced in colon cancer cells only. High levels of glucose and insulin increased cell proliferation and migration in both cell lines in vitro, mediated by Akt and PLCγ, as shown through the specific pharmacological inhibitors A6730 and U73122.CONCLUSIONS: Our molecular data explain glucose- and insulin-induced changes in a cancer cell and help to understand what might trigger tumor cell proliferation and migration in DM2 patients, too.
KW - Humans
KW - Female
KW - Cell Line, Tumor
KW - Blotting, Western
KW - Dose-Response Relationship, Drug
KW - Cell Proliferation/drug effects
KW - Enzyme Inhibitors/pharmacology
KW - Hypoglycemic Agents/pharmacology
KW - Cell Movement/drug effects
KW - Insulin/pharmacology
KW - Up-Regulation/drug effects
KW - Breast Neoplasms/metabolism/pathology
KW - Colonic Neoplasms/metabolism/pathology
KW - Estrenes/pharmacology
KW - Glucose/pharmacology
KW - Phospholipase C gamma/antagonists & inhibitors/metabolism
KW - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
KW - Pyrrolidinones/pharmacology
KW - Humans
KW - Female
KW - Cell Line, Tumor
KW - Blotting, Western
KW - Dose-Response Relationship, Drug
KW - Cell Proliferation/drug effects
KW - Enzyme Inhibitors/pharmacology
KW - Hypoglycemic Agents/pharmacology
KW - Cell Movement/drug effects
KW - Insulin/pharmacology
KW - Up-Regulation/drug effects
KW - Breast Neoplasms/metabolism/pathology
KW - Colonic Neoplasms/metabolism/pathology
KW - Estrenes/pharmacology
KW - Glucose/pharmacology
KW - Phospholipase C gamma/antagonists & inhibitors/metabolism
KW - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
KW - Pyrrolidinones/pharmacology
U2 - 10.1186/1756-0500-5-214
DO - 10.1186/1756-0500-5-214
M3 - Short publication
C2 - 22554284
VL - 5
JO - BMC RES NOTES
JF - BMC RES NOTES
SN - 1756-0500
M1 - 214
ER -
