The effects of diet induced obesity on breast cancer associated pathways in mice deficient in SFRP1

Molecular Cancer

Short Communication

Jennifer Ser-Dolansky¹  Elizabeth M Henchey¹  Josephine Wyman¹  Kelly J Gauger²  Sallie S Schneider³  Akihiko Shimono⁴  Lotfi M Bassa⁵ 

[1] Pioneer Valley Life Sciences Institute, Baystate Medical Center, 3601 Main St, 01199, Springfield, MA, USA;Pioneer Valley Life Sciences Institute, Baystate Medical Center, 3601 Main St, 01199, Springfield, MA, USA;Biology Department, University of Massachusetts, 01003, Amherst, MA, USA;Pioneer Valley Life Sciences Institute, Baystate Medical Center, 3601 Main St, 01199, Springfield, MA, USA;Veterinary and Animal Sciences, University of Massachusetts, 01003, Amherst, MA, USA;TransGenicInc., 650-0047, Kobe, Japan;Veterinary and Animal Sciences, University of Massachusetts, 01003, Amherst, MA, USA;

关键词: Sfrp1;    Obesity;    Breast cancer;    Wnt signaling;    Apoptosis;    p53;    RANKL;   

DOI  :  10.1186/1476-4598-13-117

 received in 2013-12-06, accepted in 2014-05-07,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundSecreted frizzled-related proteins (SFRPs) are a family of proteins that block the Wnt signaling pathway and loss of Sfrp1 expression is observed in breast cancer. The molecular mechanisms by which obesity contributes to breast tumorigenesis are not well defined, but involve increased inflammation. Mice deficient in Sfrp1 show enhanced mammary gland inflammation in response to diet induced obesity (DIO). Furthermore, mammary glands from Sfrp1−/− mice exhibit increased Wnt signaling, decreased cell death responses, and excessive hyper branching. The work described here was initiated to investigate whether obesity exacerbates the aforementioned pathways, as they each play a key roles in the development of breast cancer.FindingsWnt signaling is significantly affected by DIO and Sfrp1−/− loss as revealed by analysis of Myc mRNA expression and active β-catenin protein expression. Furthermore, Sfrp1−/− mice fed a high fat diet (HFD) exhibit an increase in mammary cell proliferation. The death response is also impaired in the mammary gland of Sfrp1−/− mice fed a normal diet (ND) as well as a HFD. In response to γ-irradiation, mammary glands from Sfrp1−/− mice express significantly less Bax and Bbc3 mRNA, caspase-3 positive cells, and p53 protein. The expression of Wnt4 and Tnfs11 are critical for normal progesterone mediated mammary gland development and in response to obesity, Sfrp1−/− mice express significantly more Wnt4 and Tnfs11 mRNA expression. Evaluation of progesterone receptor (PR) expression showed that DIO increases the number of PR positive cells.ConclusionsOur data indicate that the expression of Sfrp1 is a critical factor required for maintaining appropriate cellular homeostasis in response to the onset of obesity.

【 授权许可】

Unknown   
© Gauger et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.