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Role of adipocyte-derived resistin in breast cancer

[6130] Role of adipocyte-derived resistin in breast cancer.

Van Valckenborgh D, De Wever O, Hendrix A, Bracke M, Vandenbroecke R, Van Belle S, Pauwels P, Cocquyt V, Denys H

University Hospital Gent, Gent, Belgium

Background: Obesity is a known risk factor for breast cancer in postmenopausal women and the adipocyte is the most abundant cell type surrounding breast cancer cells.

The adipocyte has emerged as an active endocrine cell producing different 'adipokines', like resistin. Through in vitro and in vivo experiments, we tested the role of resistin in breast cancer tumorigenesis.

Material and Methods: For the in vitro studies we performed cell cycle analysis of MCF-7/AZ cells treated with increasing concentrations of recombinant mouse resistin (mRes) (R&D systems).

To confirm the in vitro results, we injected Swiss nu/nu mice into the mammary fat pad with stable breast cancer cell lines that produce high (MCF-7/AZ-pIRES-eGFP-high; n=10) or low amounts (MCF-7/AZ-pIRES-eGFP-low; n=10) of mRes and a control cell line (MCF-7/AZ-pIRES-eGFP-con; n=10) with no resistin expression.

Tumor volumes were determined twice a week until scarification of the mice after 7 weeks.

Results: In vitro results revealed a G1 arrest in MCF-7/AZ breast cancer cells after mRes treatment. In vivo the MCF-7/AZ-pIRES-eGFP-high cohort showed significant tumor growth inhibition (p=0,001), while the MCF-7/AZ-pIRES-eGFP-low group had intermediate tumor volumes and a greater latency period compared to the MCF-7/AZ-pIRES-eGFP-con cohort.

Discussion: We demonstrated that mouse resistin significantly inhibits tumor growth in both in vitro and in vivo experiments. Contradictory to epidemiological studies linking obesity to a higher breast cancer risk, we suggest a tumor growth inhibitory role for the adipokine resistin.

Further research is ongoing to reveal the underlying mechanisms.

San Antonio Breast Cancer Symposium, 12/06

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