Effects of adiponectin on breast cancer cell growth and signaling

• Published in: British journal of cancer Vol. 98; no. 2; pp. 370 - 379
• Main Authors: Grossmann, M E, Nkhata, K J, Mizuno, N K, Ray, A, Cleary, M P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-01-2008; Nature Publishing Group
• Subjects: Adiponectin - pharmacology; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Cell Proliferation - drug effects; Collagen Type XI - metabolism; Drug Resistance; Epidemiology; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Nude; Molecular Medicine; Neoplasms, Hormone-Dependent - pathology; Oncology; Signal Transduction - drug effects; Transfection; Translational Therapeutics; Tumor Cells, Cultured; Tumors; adiponectin; breast cancer; apoptosis; oestrogen receptor; proliferation; signalling; Cell proliferation; Estrogen receptor; Breast cancer; Malignant tumor; Adiponectin; Mammary gland diseases; Signal transduction; Cancerology; Signaling pathway; Cell death; oestrogen receptor signalling; Tumor cell; Cancer; Apoptosis; Hormonal receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604166

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-ER
α
7 cell line by insertion of ER-
α
into ER-
α
-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol
in vivo
.
In vitro
, MDA-ER
α
7 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.