Induction of mammary differentiation by mammary-derived growth inhibitor-related gene that interacts with an omega-3 fatty acid on growth inhibition of breast cancer cells.
We previously identified and characterized a novel tumor growth inhibitor and a fatty acid-binding protein in human mammary gland and named it the mammary-derived growth inhibitor-related gene (MRG). Here, the effects of MRG on mammary gland differentiation and its interaction with omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on growth inhibition were investigated. MRG protein expression was associated with human mammary gland differentiation, with the highest expression observed in the differentiated alveolar mammary epithelial cells from the lactating gland. Overexpression of MRG in human breast cancer cells induced differentiation with changes in cellular morphology and a significant increase in the production of lipid droplets. Treatment of mouse mammary gland in organ culture with MRG protein resulted in a differentiated morphology and stimulation of beta-casein expression. Treatment of human breast cancer cells with the omega-3 PUFA docosahexaenoic acid resulted in a differential growth inhibition proportional to their MRG expression. MRG-transfected cells or MRG protein treated cells were much more sensitive to docosahexaenoic acid-induced growth inhibition than MRG-negative or untreated control cells. Our results suggest that MRG is a candidate mediator of the differentiating effect of pregnancy on breast epithelial cells and may play a major role in omega-3 PUFA-mediated tumor suppression.
Wang
M
M
Department of Radiation Oncology, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Liu
Y E
YE
Ni
J
J
Aygun
B
B
Goldberg
I D
ID
Shi
Y E
YE
D001940:Breast / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007774:Lactation / Q000502:physiology
D002352:Carrier Proteins; C493408:FABP3 protein, human; C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D006131:Growth Inhibitors; D004281:Docosahexaenoic Acids