초록 ▼

본 연구에서는 지방조직에서 분비되는 Adipokines에 의한 estradiol의 대사, 생성 및 estrogen receptor 활성화 조절에 대한 포괄적인 연구를 통하여 (1. Adipokines에 의한 CYP1B1의 영향 평가:Estradiol 대사 관련 CYP1B1의 발현, 전사조절인자, ERα 의 활성, 상위신호전달체계 조사 2.Adipokines에 의한 aromatase의 영향 평가:Estradiol 생합성 관련 aromatase의 발현, 전사조절인자, COX-2와의 연관성 조사; 3. 동물의 생체내에서 CYP1B1과 a

본 연구에서는 지방조직에서 분비되는 Adipokines에 의한 estradiol의 대사, 생성 및 estrogen receptor 활성화 조절에 대한 포괄적인 연구를 통하여 (1. Adipokines에 의한 CYP1B1의 영향 평가:Estradiol 대사 관련 CYP1B1의 발현, 전사조절인자, ERα 의 활성, 상위신호전달체계 조사 2.Adipokines에 의한 aromatase의 영향 평가:Estradiol 생합성 관련 aromatase의 발현, 전사조절인자, COX-2와의 연관성 조사; 3. 동물의 생체내에서 CYP1B1과 aromatase의 영향 평가:adipokines의 생성량, estradiol 대사 및 생합성 관련 CYP1B1과 aromatase의 발현 조사) 유방암의 작용기전에 대한 신규 작용기전을 규명함으로써 지금까지 확실히 알려지지 않은 비만에 의한 estradiol 대사와 유방암의 발병 기전을 규명하였음.

Abstract ▼

Leptin is considered a novel growth factor, as it reportedly activates the proliferation of various cell types. Some studies have shown that leptin can activate breast cancer cell proliferation. Obesity is an important health concern because it is a known risk factor for breast cancer, is associated

Leptin is considered a novel growth factor, as it reportedly activates the proliferation of various cell types. Some studies have shown that leptin can activate breast cancer cell proliferation. Obesity is an important health concern because it is a known risk factor for breast cancer, is associated with a variety of metabolic disorders, and increases the risk of developing cncer. To examine the relationship between postmenopausal obesity and breast cancer, some mechanisms have been suggested, including higher levels of adipokines. The objective of this study was to determine the effect of leptin on CYP1B1 and aromatase in human breast cancer cells and high fat diet model . In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα -positive MCF-7 cells but not in ERα -negative MDA-MB-231 cells. This mechanism relates to the capacity of leptin to stimulate ERK, Akt and PKA signalling pathways, resulting in serine phosphorylation of ERα and activation of the ERE binding site in the CYP1B1 promoter. Futhermore, we examined the possible link that exists between leptin and breast cancer, focusing our attention on the effect of leptin on aromatase,which may enhance estradiol production and induce tumor cell growth stimulation. Leptin increases aromatase, is correlated with COX-2 up-regulation, mediated via the CRE activation and PKA signaling pathways in breast cancer cells.
This study investigated the high fat diet (HFD)-induced breast cancer in female rat. HFD-fed group showed that weight of body, liver, ovary, and lipid, serum level of adipokines and PGE2, breast mRNA expression of COX-2 increased. In contrast, CYP1B1 and aromatase mRNA expression don’ t changed in breast. This studies demonstrated that functional crosstalk occurs between the leptin receptor and estrogen receptor signalling pathways, which promotes breast carcinogenesis. Also, Our results contribute to the understanding of the association between obesity and breast cancer.
Since this research will establish the novel drug target networking against obesity and breast cancer, it will make a great milestone in the conquest of breast cancer diseases and provide the significant benefits to the development of clinical research.