Obesity and the associated mediators leptin, estrogen and IGF-I enhance the cell proliferation and early tumorigenesis of breast cancer cells.
Breast cancer continues to be a major cause of cancer deaths in women. Estrogen, which is also produced by the adipose tissue, is held responsible for the elevated risk of breast cancer in obese women. However, the adipose tissue secrets hormones and adipokines such as leptin and IGF-I and these substances could also contribute to an increased breast cancer risk for obese women. In this study, the impact of obesity on cell proliferation was investigated. The carcinogen 7, 12, dimethylbenz[a]anthracene (DMBA) was administered to normal weight and diet-induced obese female Sprague-Dawley rats. Cell proliferation was evaluated by immunohistological staining of BrdU-incorporation. In the mammary glands and inguinal lymphatic nodes of the obese rats, cell proliferation was significantly increased, indicating a significant influence of obesity on breast cancer. Effects of leptin, estrogen, and IGF-I on the proliferation of MCF-7 cells in vitro were assessed using an MTT assay. Cell culture experiments demonstrated a mitogenic role of these three mediators on cell proliferation. Our data demonstrate a stimulative effect of substances produced by the adipose tissue on breast cancer. Body weight specific cell proliferation suggests that obesity-related adipokines and mediators enhance cell proliferation and increase the risk for breast cancer.
Institute for Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Anne
A
Lautenbach
Anne
A
Budde
Christiane D
CD
Wrann
Birgit
B
Teichmann
Gertrud
G
Vieten
Tim
T
Karl
Heike
H
Nave
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D001943:Breast Neoplasms / Q000473:pathology; D002273:Carcinogens; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006119:Groin; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002273:Carcinogens; D004041:Dietary Fats; D020738:Leptin; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I