Year: 2014
Type: dissertation
Abstract: Social isolation is a potent psychosocial stressor and is associated with obesity and increased breast cancer risk and mortality.In this thesis, I investigated the combined effects of social isolation stress and obesity on insulin resistance, mammary tumorigenesis, and the mechanisms involved.First, I studied the effects of social isolation stress in combination with an obesity inducing diet (OID) on mammary tumorigenesis induced by medroxyprogesterone acetate (MPA) and 7,12dimethylbenz(a)anthracene (DMBA) in female C57BL/6 mice.Social isolation, with or without OID, increased food intake and body weight, and caused impaired insulin and glucose tolerance.Serum NPY levels were increased only in socially isolated OID fed mice, whilst adiponectin levels were reduced both by OID and social isolation.These changes may have contributed to insulin resistance.Mammary tumorigenesis was significantly higher in the socially isolated OID fed mice than in group-housed obese or control mice.Consistent with a previous study indicating that social isolation does not increase mammary tumorigenesis in p53 knockout mice, we found an increase in p53 mRNA expression in socially-isolated mice that exhibited increased mammary cancer risk.Apoptosis was not altered in these mice, but cell proliferation was significantly increased.Social isolation increased the expression of p53-induced autophagy-linked genes and other genes indicative of autophagy in the mammary gland.In summary, we found that obesity I would like to dedicate the whole of this work to my father, Dale M. Sumis.He was diagnosed with cancer when I was a teenager, and while it has been over ten years now since he passed away, his absence in my life will never be filled or forgotten.I miss you.In loving memory, Allison M.
Author: Allison Sumis
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W601310209