Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells

B. Majumder, K. W. Wahle, Susan Emma Moir, Andrew Craig Schofield, S. N. Choe, A. J. Farquharson, I. Grant, Steven Darryll Heys

Research output: Contribution to journalArticle

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Abstract

Conjugated linoleic acid (CLA) reduces mammary tumorigenesis in rodent models, induces apoptosis in rodent mammary tumor cell lines, and decreases expression of antiapoptotic bcl-2 in rat mammary tissue. This investigation focused on the cell mechanisms underlying the antitumor effects of CLA. Changes (mRNA, protein) in expression of major proapoptotic p53, p21WAF1/CIP1, bax, bcl-Xs genes, and the antiapoptotic bcl-2 gene were observed in malignant MCF-7 and MDA-MB-231 cells and in benign MCF-10a human mammary tumor cells in culture. CLA, but not linoleic acid (LA), inhibited proliferation in all cells; CLA mix was most effective. CLA increased DNA damage (apoptosis). CLA increased mRNA expression of p53 and p21WAF1/CIP1 (three- to fivefold and twofold, respectively) but either decreased bcl-2 by 20-30% or had no effect in MCF-7 and MCF-10a cells, respectively; protein expression reflected mRNA values. In MDA-MBA-231 (mutant p53) cells, mRNA for p53 was not changed, but p21WAF1/CIP1 and bcl-2 mRNA was increased. Protein expression largely reflected mRNA changes but, surprisingly, CLA completely suppressed mutant p53 protein in MDA-MB-231 cells. Apparent antiapoptotic effects of increased bcl-2 expression in MDA-MBA-231 cells were countered by increased proapoptotic p21WAF1/CIP1, Bax, and Bcl-Xs proteins. Findings indicate that CLA elicits mainly proapoptotic effects in human breast tumor cells through both p53-dependent and p53-independent pathways, according to cell type.

Original languageEnglish
Pages (from-to)1447-1449
Number of pages2
JournalThe FASEB Journal
Volume16
Issue number11
DOIs
Publication statusPublished - Jul 2002

Keywords

  • mammary cancer
  • apoptotic gene expression
  • antiapoptotic gene expression
  • MAMMARY EPITHELIAL-CELLS
  • EICOSAPENTAENOIC ACID
  • POOR RESPONSE
  • BCL-2
  • RISK
  • CHEMOTHERAPY
  • PROTEIN
  • DIET
  • CONSUMPTION
  • PREVENTION

Cite this

Majumder, B., Wahle, K. W., Moir, S. E., Schofield, A. C., Choe, S. N., Farquharson, A. J., ... Heys, S. D. (2002). Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells. The FASEB Journal, 16(11), 1447-1449. https://doi.org/10.1096/FJ.01-0720FJE

Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells. / Majumder, B.; Wahle, K. W.; Moir, Susan Emma; Schofield, Andrew Craig; Choe, S. N.; Farquharson, A. J.; Grant, I.; Heys, Steven Darryll.

In: The FASEB Journal, Vol. 16, No. 11, 07.2002, p. 1447-1449.

Research output: Contribution to journalArticle

Majumder, B, Wahle, KW, Moir, SE, Schofield, AC, Choe, SN, Farquharson, AJ, Grant, I & Heys, SD 2002, 'Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells' The FASEB Journal, vol. 16, no. 11, pp. 1447-1449. https://doi.org/10.1096/FJ.01-0720FJE
Majumder, B. ; Wahle, K. W. ; Moir, Susan Emma ; Schofield, Andrew Craig ; Choe, S. N. ; Farquharson, A. J. ; Grant, I. ; Heys, Steven Darryll. / Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells. In: The FASEB Journal. 2002 ; Vol. 16, No. 11. pp. 1447-1449.
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abstract = "Conjugated linoleic acid (CLA) reduces mammary tumorigenesis in rodent models, induces apoptosis in rodent mammary tumor cell lines, and decreases expression of antiapoptotic bcl-2 in rat mammary tissue. This investigation focused on the cell mechanisms underlying the antitumor effects of CLA. Changes (mRNA, protein) in expression of major proapoptotic p53, p21WAF1/CIP1, bax, bcl-Xs genes, and the antiapoptotic bcl-2 gene were observed in malignant MCF-7 and MDA-MB-231 cells and in benign MCF-10a human mammary tumor cells in culture. CLA, but not linoleic acid (LA), inhibited proliferation in all cells; CLA mix was most effective. CLA increased DNA damage (apoptosis). CLA increased mRNA expression of p53 and p21WAF1/CIP1 (three- to fivefold and twofold, respectively) but either decreased bcl-2 by 20-30{\%} or had no effect in MCF-7 and MCF-10a cells, respectively; protein expression reflected mRNA values. In MDA-MBA-231 (mutant p53) cells, mRNA for p53 was not changed, but p21WAF1/CIP1 and bcl-2 mRNA was increased. Protein expression largely reflected mRNA changes but, surprisingly, CLA completely suppressed mutant p53 protein in MDA-MB-231 cells. Apparent antiapoptotic effects of increased bcl-2 expression in MDA-MBA-231 cells were countered by increased proapoptotic p21WAF1/CIP1, Bax, and Bcl-Xs proteins. Findings indicate that CLA elicits mainly proapoptotic effects in human breast tumor cells through both p53-dependent and p53-independent pathways, according to cell type.",
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T1 - Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells

AU - Majumder, B.

AU - Wahle, K. W.

AU - Moir, Susan Emma

AU - Schofield, Andrew Craig

AU - Choe, S. N.

AU - Farquharson, A. J.

AU - Grant, I.

AU - Heys, Steven Darryll

PY - 2002/7

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N2 - Conjugated linoleic acid (CLA) reduces mammary tumorigenesis in rodent models, induces apoptosis in rodent mammary tumor cell lines, and decreases expression of antiapoptotic bcl-2 in rat mammary tissue. This investigation focused on the cell mechanisms underlying the antitumor effects of CLA. Changes (mRNA, protein) in expression of major proapoptotic p53, p21WAF1/CIP1, bax, bcl-Xs genes, and the antiapoptotic bcl-2 gene were observed in malignant MCF-7 and MDA-MB-231 cells and in benign MCF-10a human mammary tumor cells in culture. CLA, but not linoleic acid (LA), inhibited proliferation in all cells; CLA mix was most effective. CLA increased DNA damage (apoptosis). CLA increased mRNA expression of p53 and p21WAF1/CIP1 (three- to fivefold and twofold, respectively) but either decreased bcl-2 by 20-30% or had no effect in MCF-7 and MCF-10a cells, respectively; protein expression reflected mRNA values. In MDA-MBA-231 (mutant p53) cells, mRNA for p53 was not changed, but p21WAF1/CIP1 and bcl-2 mRNA was increased. Protein expression largely reflected mRNA changes but, surprisingly, CLA completely suppressed mutant p53 protein in MDA-MB-231 cells. Apparent antiapoptotic effects of increased bcl-2 expression in MDA-MBA-231 cells were countered by increased proapoptotic p21WAF1/CIP1, Bax, and Bcl-Xs proteins. Findings indicate that CLA elicits mainly proapoptotic effects in human breast tumor cells through both p53-dependent and p53-independent pathways, according to cell type.

AB - Conjugated linoleic acid (CLA) reduces mammary tumorigenesis in rodent models, induces apoptosis in rodent mammary tumor cell lines, and decreases expression of antiapoptotic bcl-2 in rat mammary tissue. This investigation focused on the cell mechanisms underlying the antitumor effects of CLA. Changes (mRNA, protein) in expression of major proapoptotic p53, p21WAF1/CIP1, bax, bcl-Xs genes, and the antiapoptotic bcl-2 gene were observed in malignant MCF-7 and MDA-MB-231 cells and in benign MCF-10a human mammary tumor cells in culture. CLA, but not linoleic acid (LA), inhibited proliferation in all cells; CLA mix was most effective. CLA increased DNA damage (apoptosis). CLA increased mRNA expression of p53 and p21WAF1/CIP1 (three- to fivefold and twofold, respectively) but either decreased bcl-2 by 20-30% or had no effect in MCF-7 and MCF-10a cells, respectively; protein expression reflected mRNA values. In MDA-MBA-231 (mutant p53) cells, mRNA for p53 was not changed, but p21WAF1/CIP1 and bcl-2 mRNA was increased. Protein expression largely reflected mRNA changes but, surprisingly, CLA completely suppressed mutant p53 protein in MDA-MB-231 cells. Apparent antiapoptotic effects of increased bcl-2 expression in MDA-MBA-231 cells were countered by increased proapoptotic p21WAF1/CIP1, Bax, and Bcl-Xs proteins. Findings indicate that CLA elicits mainly proapoptotic effects in human breast tumor cells through both p53-dependent and p53-independent pathways, according to cell type.

KW - mammary cancer

KW - apoptotic gene expression

KW - antiapoptotic gene expression

KW - MAMMARY EPITHELIAL-CELLS

KW - EICOSAPENTAENOIC ACID

KW - POOR RESPONSE

KW - BCL-2

KW - RISK

KW - CHEMOTHERAPY

KW - PROTEIN

KW - DIET

KW - CONSUMPTION

KW - PREVENTION

U2 - 10.1096/FJ.01-0720FJE

DO - 10.1096/FJ.01-0720FJE

M3 - Article

VL - 16

SP - 1447

EP - 1449

JO - The FASEB Journal

JF - The FASEB Journal

SN - 0892-6638

IS - 11

ER -