Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies.
BACKGROUND
Obesity is a major risk factor for breast cancer. We hypothesized that obesity-induced decreases in total and/or high-molecular-weight (HMW) adiponectin levels may underlie this association.


METHODS
We measured serum total and HMW adiponectin in a hospital-based case-control study of 74 female breast cancer patients and 76 controls. In parallel, expression of adiponectin and its receptors AdipoR1/R2 were measured in tissue samples using RT-PCR, and protein expression of AdipoR1/R2 was localized and quantified using immunohistochemistry. Finally, we documented AdipoR1/R2 expression in several breast cancer cell lines and studied adiponectin signaling and the effect of adiponectin on proliferation in the T47D breast cancer cell line in vitro.


RESULTS
Women with the highest adiponectin levels had a 65% reduced risk of breast cancer (P = 0.04). This association became stronger after adjustment for age, body mass index, and hormonal and reproductive factors (P = 0.02). Modeling HMW instead of total adiponectin produced similar results and did not offer any additional predictive value. Breast cancer cells expressed AdipoR1/R2 but not adiponectin. Expression of AdipoR1, but not AdipoR2, was higher in tumor tissue than both adjacent and control tissues. Exposure of T47D cells to adiponectin significantly inhibited the percentage of viable cells to 86% and proliferation to 66% but had no effect on apoptosis. These effects were associated with activation of ERK1/2 but not AMP-activated protein kinase or p38MAPK.


CONCLUSIONS
These studies suggest that adiponectin may act as a biomarker of carcinogenesis and may constitute a molecular link between obesity and breast cancer.
Körner
Antje
A
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Stoneman 816, Boston, Massachusetts 02215, USA.
Pazaitou-Panayiotou
Kalliopi
K
Kelesidis
Theodoros
T
Kelesidis
Iosif
I
Williams
Catherine J
CJ
Kaprara
Athina
A
Bullen
John
J
Neuwirth
Anke
A
Tseleni
Sofia
S
Mitsiades
Nicholas
N
Kiess
Wieland
W
Mantzoros
Christos S
CS
D052242:Adiponectin / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism; D002277:Carcinoma / Q000097:blood* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism; D014018:Tissue Distribution
C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface