Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum.

Research output: Contribution to journalJournal articlepeer-review

Standard

Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum. / Wlodarski, Pawel; Kasprzycka, Monika; Liu, Xiaobin; Marzec, Michal; Robertson, Erle S.; Slupianek, Artur; Wasik, Mariusz A.

In: Cancer Research, Vol. 65, No. 17, 2005, p. 7800-7808.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Wlodarski, P, Kasprzycka, M, Liu, X, Marzec, M, Robertson, ES, Slupianek, A & Wasik, MA 2005, 'Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum.', Cancer Research, vol. 65, no. 17, pp. 7800-7808. https://doi.org/10.1158/0008-5472.CAN-04-4180

APA

Wlodarski, P., Kasprzycka, M., Liu, X., Marzec, M., Robertson, E. S., Slupianek, A., & Wasik, M. A. (2005). Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum. Cancer Research, 65(17), 7800-7808. https://doi.org/10.1158/0008-5472.CAN-04-4180

Vancouver

Wlodarski P, Kasprzycka M, Liu X, Marzec M, Robertson ES, Slupianek A et al. Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum. Cancer Research. 2005;65(17):7800-7808. https://doi.org/10.1158/0008-5472.CAN-04-4180

Author

Wlodarski, Pawel ; Kasprzycka, Monika ; Liu, Xiaobin ; Marzec, Michal ; Robertson, Erle S. ; Slupianek, Artur ; Wasik, Mariusz A. / Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum. In: Cancer Research. 2005 ; Vol. 65, No. 17. pp. 7800-7808.

Bibtex

@article{2f8e019de2624f5996e1080eb36821b8,
title = "Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum.",
abstract = "The study examines the preponderance and mechanism of mammalian target of rapamycin (mTOR) activation in three distinct types of transformed B lymphocytes that differ in expression of the EBV genome. All three types [EBV-immortalized cells that express a broad spectrum of the virus-encoded genes (type III latency; EBV+/III), EBV-pos. cells that express only a subset of the EBV-encoded genes (EBV+/I), and EBV-neg., germinal center-derived cells (EBV-)] universally displayed activation of the mTOR signaling pathway. However, only the EBV+/III transformed B cells displayed also activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that is considered to be the key activator of mTOR and of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway that coactivates one of the immediate targets of mTOR, p70 S6K1. Activation of the PI3K/Akt and MEK/ERK, but not of the mTOR pathway, was inhibited by serum withdrawal and restored by insulin growth factor-I. In contrast, activation of mTOR, but not PI3K/Akt and MEK/ERK, was sensitive to nutrient depletion. Both direct Akt (Akt inhibitors I-III) and a PI3K inhibitor (wortmannin at 1 nmol/L) suppressed Akt phosphorylation without significantly affecting mTOR activation. Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. U0126, a MEK inhibitor, had a moderate antiproliferative effect only on the EBV+/III cells. These results indicate that mTOR kinase activation is mediated in the transformed B cells by the mechanism(s) independent of the PI3K/Akt signaling pathway. They also suggest that inhibition of mTOR signaling might be effective in therapy of the large spectrum of B-cell lymphomas. [on SciFinder(R)]",
keywords = "B lymphocyte nutrient signaling transformation IGF lymphoma",
author = "Pawel Wlodarski and Monika Kasprzycka and Xiaobin Liu and Michal Marzec and Robertson, {Erle S.} and Artur Slupianek and Wasik, {Mariusz A.}",
note = "M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved. CAPLUS AN 2005:972191(Journal)",
year = "2005",
doi = "10.1158/0008-5472.CAN-04-4180",
language = "English",
volume = "65",
pages = "7800--7808",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "17",

}

RIS

TY - JOUR

T1 - Activation of Mammalian Target of Rapamycin in Transformed B Lymphocytes Is Nutrient Dependent but Independent of Akt, Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase, Insulin Growth Factor-I, and Serum.

AU - Wlodarski, Pawel

AU - Kasprzycka, Monika

AU - Liu, Xiaobin

AU - Marzec, Michal

AU - Robertson, Erle S.

AU - Slupianek, Artur

AU - Wasik, Mariusz A.

N1 - M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved. CAPLUS AN 2005:972191(Journal)

PY - 2005

Y1 - 2005

N2 - The study examines the preponderance and mechanism of mammalian target of rapamycin (mTOR) activation in three distinct types of transformed B lymphocytes that differ in expression of the EBV genome. All three types [EBV-immortalized cells that express a broad spectrum of the virus-encoded genes (type III latency; EBV+/III), EBV-pos. cells that express only a subset of the EBV-encoded genes (EBV+/I), and EBV-neg., germinal center-derived cells (EBV-)] universally displayed activation of the mTOR signaling pathway. However, only the EBV+/III transformed B cells displayed also activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that is considered to be the key activator of mTOR and of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway that coactivates one of the immediate targets of mTOR, p70 S6K1. Activation of the PI3K/Akt and MEK/ERK, but not of the mTOR pathway, was inhibited by serum withdrawal and restored by insulin growth factor-I. In contrast, activation of mTOR, but not PI3K/Akt and MEK/ERK, was sensitive to nutrient depletion. Both direct Akt (Akt inhibitors I-III) and a PI3K inhibitor (wortmannin at 1 nmol/L) suppressed Akt phosphorylation without significantly affecting mTOR activation. Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. U0126, a MEK inhibitor, had a moderate antiproliferative effect only on the EBV+/III cells. These results indicate that mTOR kinase activation is mediated in the transformed B cells by the mechanism(s) independent of the PI3K/Akt signaling pathway. They also suggest that inhibition of mTOR signaling might be effective in therapy of the large spectrum of B-cell lymphomas. [on SciFinder(R)]

AB - The study examines the preponderance and mechanism of mammalian target of rapamycin (mTOR) activation in three distinct types of transformed B lymphocytes that differ in expression of the EBV genome. All three types [EBV-immortalized cells that express a broad spectrum of the virus-encoded genes (type III latency; EBV+/III), EBV-pos. cells that express only a subset of the EBV-encoded genes (EBV+/I), and EBV-neg., germinal center-derived cells (EBV-)] universally displayed activation of the mTOR signaling pathway. However, only the EBV+/III transformed B cells displayed also activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that is considered to be the key activator of mTOR and of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway that coactivates one of the immediate targets of mTOR, p70 S6K1. Activation of the PI3K/Akt and MEK/ERK, but not of the mTOR pathway, was inhibited by serum withdrawal and restored by insulin growth factor-I. In contrast, activation of mTOR, but not PI3K/Akt and MEK/ERK, was sensitive to nutrient depletion. Both direct Akt (Akt inhibitors I-III) and a PI3K inhibitor (wortmannin at 1 nmol/L) suppressed Akt phosphorylation without significantly affecting mTOR activation. Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. U0126, a MEK inhibitor, had a moderate antiproliferative effect only on the EBV+/III cells. These results indicate that mTOR kinase activation is mediated in the transformed B cells by the mechanism(s) independent of the PI3K/Akt signaling pathway. They also suggest that inhibition of mTOR signaling might be effective in therapy of the large spectrum of B-cell lymphomas. [on SciFinder(R)]

KW - B lymphocyte nutrient signaling transformation IGF lymphoma

U2 - 10.1158/0008-5472.CAN-04-4180

DO - 10.1158/0008-5472.CAN-04-4180

M3 - Journal article

VL - 65

SP - 7800

EP - 7808

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 17

ER -

ID: 202376216