Grossmann M E, Nkhata K J, Mizuno N K, Ray A, Cleary M P
Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Br J Cancer. 2008 Jan 29;98(2):370-9. doi: 10.1038/sj.bjc.6604166. Epub 2008 Jan 8.
Obesity is a risk factor for postmenopausal breast cancer. Adiponectin/Acrp30 is lower in obese individuals and may be negatively regulating breast cancer growth. Here we determined that five breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, T47D, and SK-BR-3, expressed one or both of the Acrp30 receptors. In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth. Oestrogen receptor (ER) positive MCF-7 and T47D cells were inhibited at lower Acrp30 concentrations than ER-negative SK-BR-3 cells. Growth inhibition may be related to apoptosis since PARP cleavage was increased by Acrp30 in the ER-positive cell lines. To investigate the role of ER in the response of breast cancer cells to Acrp30, we established the MDA-ERalpha7 cell line by insertion of ER-alpha into ER-alpha-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol in vivo. In vitro, MDA-ERalpha7 cells were growth inhibited by globular Acrp30 while the parental cells were not. This inhibition appeared to be due to blockage of JNK2 signalling. These results provide information on how obesity may influence breast cancer cell proliferation and establish a new model to examine interactions between ER and Acrp30.
肥胖是绝经后乳腺癌的一个风险因素。脂联素/Acrp30在肥胖个体中水平较低，可能对乳腺癌生长起负调控作用。在此，我们确定了五种乳腺癌细胞系，即MDA-MB-231、MDA-MB-361、MCF-7、T47D和SK-BR-3，表达一种或两种Acrp30受体。此外，我们发现向MCF-7、T47D和SK-BR-3细胞系中添加Acrp30会抑制其生长。雌激素受体（ER）阳性的MCF-7和T47D细胞在较低的Acrp30浓度下就受到抑制，而ER阴性的SK-BR-3细胞则不然。生长抑制可能与细胞凋亡有关，因为在ER阳性细胞系中，Acrp30会增加PARP的裂解。为了研究ER在乳腺癌细胞对Acrp30反应中的作用，我们通过将ER-α插入ER-α阴性的MDA-MB-231细胞中，建立了MDA-ERalpha7细胞系。该细胞系在无胸腺小鼠中易于形成肿瘤，且在体内对雌二醇有反应。在体外，球状Acrp30可抑制MDA-ERalpha7细胞的生长，而亲本细胞则不受影响。这种抑制作用似乎是由于JNK2信号通路受阻所致。这些结果提供了关于肥胖如何影响乳腺癌细胞增殖的信息，并建立了一个新模型来研究ER与Acrp30之间的相互作用。
