Conjugated linoleic acid (CLA) up-regulates the estrogen-regulated cancer suppressor gene, protein tyrosine phosphatase gamma (PTPgama), in human breast cells.
BACKGROUND
Conjugated linoleic acid (CLA), a naturally occurring compound found in ruminants products, has been shown to possess anticancer properties in vivo and in vitro. There are several CLA isomers in ruminant-produced foods, among which t10, c12-CLA and c9, t11-CLA are the most potent. Protein tyrosine phosphatase gamma (PTPgamma) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicated that estradiol-17beta (E2)-induced suppression of PTPgamma may play a role in mammary tumorigenesis.


METHODS
The effects of t10, c12-CLA and c9, t11-CLA on PTPgamma mRNA expression in human breast epithelial cells and stromal cells, isolated from surgical specimens of mammoplasty and breast cancer patients, were detected and quantified by RT-PCR RESULTS: The PTPgamma mRNA expression was lower in cancer than in normal breast cells. Both t10, c12-CLA and c9, t11-CLA significantly (p < 0.05) increased the PTPgamma mRNA levels in primary cultured normal breast epithelial cells, normal breast stromal cells and breast cancer epithelial cells, but not in breast cancer stromal cells. t10, c12-CLA appeared to be the most active isomer in estrogen receptor a (ERalpha)-positive human breast cancer epithelial cells.


CONCLUSIONS
The results indicate that dietary CLA might serve as a chemo-preventive and chemo-therapeutic agent in human breast cancers by up-regulating the estrogen-regulated tumor suppressor gene, PTPgamma expression.
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Li-Shu
LS
Wang
Yi-Wen
YW
Huang
Yasuro
Y
Sugimoto
Suling
S
Liu
Hsiang-Lin
HL
Chang
Weiping
W
Ye
Sherry
S
Shu
Young C
YC
Lin
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects
D047628:Estrogen Receptor alpha; D044243:Linoleic Acids, Conjugated; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; C516850:PTPRG protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5