Adipocyte culture medium stimulates production of macrophage inhibitory cytokine 1 in MDA-MB-231 cells.
Obesity is one of the potential risk factors in causing breast cancer. As a result, adipose tissue surrounding breast ductal cells may play an important role in the breast cancer development or progression. To identify the genes that are regulated by factors secreted from adipocytes in breast cancer cells, MDA-MB-231 cells were treated with the culture medium of adipocytes. Most of induced genes were related to immune function and wound healing, which share a common gene expression signature with cancer progression. In present study macrophage inhibitory cytokine 1 (MIC-1) gene was studied among the induced genes. It was found that both MIC-1 mRNA and protein were dramatically increased by the culture medium of adipocytes. Furthermore, proteinase K-treated adipocyte culture supernatants also induced MIC-1 expression. These findings indicate that proteins are not major MIC-1 inducing factors in adipocyte culture medium. Consequently, we examined the effect of free fatty acids such as palmitate and oleate on MIC-1 induction and found that palmitate markedly induced MIC-1 gene expression, whereas oleate did not. Adipocyte culture medium- and palmitate-induced MIC-1 gene expression was mediated by the activation of p38 MAPK, but not by the activation of JNK, ERK, and NF-kappaB pathway. In addition, adipocyte-CM-induced MIC-1 also increased invasiveness of MDA-MB-231 cells.
Kim
Jae Hyeong
JH
Research Center for Women's Disease, Department of Life Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Kim
Kun-yong
KY
Jeon
Jun Ho
JH
Lee
Su Hee
SH
Hwang
Ji-Eun
JE
Lee
Jung Hyeong
JH
Kim
Kwang Kyu
KK
Lim
Jong-Seok
JS
Kim
Keun Il
KI
Moon
Eun-Yi
EY
Lee
Hee Gu
HG
Ryu
Jae-Ha
JH
Yang
Young
Y
D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055436:Growth Differentiation Factor 15; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D010168:Palmitates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D003470:Culture Media; D016207:Cytokines; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D016328:NF-kappa B; D010168:Palmitates; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases