Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine

Valentina K. Todorova, Yihong Kaufmann, Shaoke Luo, Vicki Klimberg

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Previous studies established that oral glutamine (GLN) reduced tumor development in implantable and 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer models. This finding was associated with a decrease in tumor glutathione (GSH) levels, while maintaining normal gut, blood, and breast GSH. Alterations in GSH levels contribute to the control of apoptotic and cell cycle-regulating signaling. The aim of this study was to examine the role of dietary GLN on activation of p53 and c-myc, which play critical roles in cancer development and sensitivity to radiation and chemotherapy. Mammary gland carcinomas were induced in rats by DMBA. The rats were gavaged daily with GLN or water (controls), starting 1 wk prior DMBA-application and throughout the duration of the experiment (11 wk after DMBA). Tumor DNA wax examined for mutations in p53 exons 5 and 6. Protein and mRNA levels of p53, p21WAF1/CIP1, PTEN, IGF-IR, mdm2, and c-myc in tumors of GLN-supplemented rats were compared with those of the control rats (received water). The sequencing of p53 showed that it was wild type. Increased phosphorylation of p53, as well as higher mRNA and protein levels of p21WAF1/CIP1, PTEN, and mdm2, and lower levels of IGF-IR were detected in tumors of GLN-supplemented rats vs. controls. Both phoxphorylated c-myc and c-myc mRNA levels were reduced by GLN. The up-regulation of tumor p53 signaling and down-regulation of c-myc, in addition to previously established inhibition of Akt signaling in DMBA-breast cancer model, suggest that dietary GLN could be a useful approach for increasing the effectiveness of cancer treatment.

Original languageEnglish (US)
Pages (from-to)263-273
Number of pages11
JournalNutrition and Cancer
Volume54
Issue number2
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

9,10-Dimethyl-1,2-benzanthracene
Glutamine
Breast Neoplasms
Neoplasms
Messenger RNA
Water
Waxes
Radiation Tolerance
Human Mammary Glands
Cell Cycle Checkpoints
Glutathione
Exons
Proteins
Breast
Up-Regulation
Down-Regulation
Phosphorylation
Drug Therapy
Mutation
DNA

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

Cite this

Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine. / Todorova, Valentina K.; Kaufmann, Yihong; Luo, Shaoke; Klimberg, Vicki.

In: Nutrition and Cancer, Vol. 54, No. 2, 2006, p. 263-273.

Research output: Contribution to journalArticle

Todorova, Valentina K. ; Kaufmann, Yihong ; Luo, Shaoke ; Klimberg, Vicki. / Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine. In: Nutrition and Cancer. 2006 ; Vol. 54, No. 2. pp. 263-273.
@article{86a403343a2b4fc28c43cde2f26fd5f0,
title = "Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine",
abstract = "Previous studies established that oral glutamine (GLN) reduced tumor development in implantable and 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer models. This finding was associated with a decrease in tumor glutathione (GSH) levels, while maintaining normal gut, blood, and breast GSH. Alterations in GSH levels contribute to the control of apoptotic and cell cycle-regulating signaling. The aim of this study was to examine the role of dietary GLN on activation of p53 and c-myc, which play critical roles in cancer development and sensitivity to radiation and chemotherapy. Mammary gland carcinomas were induced in rats by DMBA. The rats were gavaged daily with GLN or water (controls), starting 1 wk prior DMBA-application and throughout the duration of the experiment (11 wk after DMBA). Tumor DNA wax examined for mutations in p53 exons 5 and 6. Protein and mRNA levels of p53, p21WAF1/CIP1, PTEN, IGF-IR, mdm2, and c-myc in tumors of GLN-supplemented rats were compared with those of the control rats (received water). The sequencing of p53 showed that it was wild type. Increased phosphorylation of p53, as well as higher mRNA and protein levels of p21WAF1/CIP1, PTEN, and mdm2, and lower levels of IGF-IR were detected in tumors of GLN-supplemented rats vs. controls. Both phoxphorylated c-myc and c-myc mRNA levels were reduced by GLN. The up-regulation of tumor p53 signaling and down-regulation of c-myc, in addition to previously established inhibition of Akt signaling in DMBA-breast cancer model, suggest that dietary GLN could be a useful approach for increasing the effectiveness of cancer treatment.",
author = "Todorova, {Valentina K.} and Yihong Kaufmann and Shaoke Luo and Vicki Klimberg",
year = "2006",
doi = "10.1207/s15327914nc5402_13",
language = "English (US)",
volume = "54",
pages = "263--273",
journal = "Nutrition and Cancer",
issn = "0163-5581",
publisher = "Routledge",
number = "2",

}

TY - JOUR

T1 - Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine

AU - Todorova, Valentina K.

AU - Kaufmann, Yihong

AU - Luo, Shaoke

AU - Klimberg, Vicki

PY - 2006

Y1 - 2006

N2 - Previous studies established that oral glutamine (GLN) reduced tumor development in implantable and 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer models. This finding was associated with a decrease in tumor glutathione (GSH) levels, while maintaining normal gut, blood, and breast GSH. Alterations in GSH levels contribute to the control of apoptotic and cell cycle-regulating signaling. The aim of this study was to examine the role of dietary GLN on activation of p53 and c-myc, which play critical roles in cancer development and sensitivity to radiation and chemotherapy. Mammary gland carcinomas were induced in rats by DMBA. The rats were gavaged daily with GLN or water (controls), starting 1 wk prior DMBA-application and throughout the duration of the experiment (11 wk after DMBA). Tumor DNA wax examined for mutations in p53 exons 5 and 6. Protein and mRNA levels of p53, p21WAF1/CIP1, PTEN, IGF-IR, mdm2, and c-myc in tumors of GLN-supplemented rats were compared with those of the control rats (received water). The sequencing of p53 showed that it was wild type. Increased phosphorylation of p53, as well as higher mRNA and protein levels of p21WAF1/CIP1, PTEN, and mdm2, and lower levels of IGF-IR were detected in tumors of GLN-supplemented rats vs. controls. Both phoxphorylated c-myc and c-myc mRNA levels were reduced by GLN. The up-regulation of tumor p53 signaling and down-regulation of c-myc, in addition to previously established inhibition of Akt signaling in DMBA-breast cancer model, suggest that dietary GLN could be a useful approach for increasing the effectiveness of cancer treatment.

AB - Previous studies established that oral glutamine (GLN) reduced tumor development in implantable and 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer models. This finding was associated with a decrease in tumor glutathione (GSH) levels, while maintaining normal gut, blood, and breast GSH. Alterations in GSH levels contribute to the control of apoptotic and cell cycle-regulating signaling. The aim of this study was to examine the role of dietary GLN on activation of p53 and c-myc, which play critical roles in cancer development and sensitivity to radiation and chemotherapy. Mammary gland carcinomas were induced in rats by DMBA. The rats were gavaged daily with GLN or water (controls), starting 1 wk prior DMBA-application and throughout the duration of the experiment (11 wk after DMBA). Tumor DNA wax examined for mutations in p53 exons 5 and 6. Protein and mRNA levels of p53, p21WAF1/CIP1, PTEN, IGF-IR, mdm2, and c-myc in tumors of GLN-supplemented rats were compared with those of the control rats (received water). The sequencing of p53 showed that it was wild type. Increased phosphorylation of p53, as well as higher mRNA and protein levels of p21WAF1/CIP1, PTEN, and mdm2, and lower levels of IGF-IR were detected in tumors of GLN-supplemented rats vs. controls. Both phoxphorylated c-myc and c-myc mRNA levels were reduced by GLN. The up-regulation of tumor p53 signaling and down-regulation of c-myc, in addition to previously established inhibition of Akt signaling in DMBA-breast cancer model, suggest that dietary GLN could be a useful approach for increasing the effectiveness of cancer treatment.

UR - http://www.scopus.com/inward/record.url?scp=33748132632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748132632&partnerID=8YFLogxK

U2 - 10.1207/s15327914nc5402_13

DO - 10.1207/s15327914nc5402_13

M3 - Article

VL - 54

SP - 263

EP - 273

JO - Nutrition and Cancer

JF - Nutrition and Cancer

SN - 0163-5581

IS - 2

ER -