Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line

被引:233
|
作者
Catalano, S
Marsico, S
Giordano, C
Mauro, L
Rizza, P
Panno, ML
Andò, S
机构
[1] Univ Calabria, Dept Cell Biol, Fac Pharm, I-87030 Arcavacata di Rende CS, Italy
[2] Univ Calabria, Ctr Sanitario, Fac Pharm, I-87030 Arcavacata di Rende CS, Italy
[3] Univ Calabria, Dept Pharmacobiol, Fac Pharm, I-87030 Arcavacata di Rende CS, Italy
[4] Univ Calabria, Dept Cell Biol, Fac Pharm, I-87030 Arcavacata di Rende CS, Italy
关键词
D O I
10.1074/jbc.M301695200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Leptin, a product of adipocytes, is involved in the regulation of body weight and results strongly correlated to body fat content. An excess of fat mass represents a breast cancer risk factor particularly in postmenopausal women, where estrogen production by adipose tissue through its own aromatase activity stimulates tumor progression. Leptin stimulates estrogen production through the increase of aromatase expression and activity in human luteinized granulosa cells and adipose stromal cells. In the present study, we have examined the possible link that exists between leptin and breast cancer, focusing our attention on the direct effect of leptin on aromatase activity, which may enhance estrogen production and induce tumor cell growth stimulation. We have shown that leptin enhances aromatase mRNA expression, aromatase content, and its enzymatic activity in MCF-7. Aromatase expression appears to be regulated by tissue-specific promoter. It has been demonstrated that promoters II and 1.3 are the major promoters that drive aromatase expression in MCF-7. Transient transfection experiments using vector containing human aromatase promoters II and 1.3 sequence fused with luciferase reporter gene demonstrated that leptin is able to activate this promoter. In the presence of either mitogen-activated protein kinase inhibitor PD 98059 or ERK2 dominant negative as well as in the presence of STAT3 dominant negative, the stimulatory effects of leptin on aromatase promoter, enzymatic activity, and aromatase protein content were inhibited. Functional studies of mutagenesis and electrophoretic mobility shift assay revealed that the AP-1 motif is important in determining the up-regulatory effects induced by leptin on aromatase expression in MCF-7.
引用
收藏
页码:28668 / 28676
页数:9
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