Role of Obesity in Prostate Cancer Development

摘要

Prospective epidemiological studies suggest that obesity increases the risk for prostate cancer. Also, mortality from prostate cancer is increased with elevated body weights and several recent studies have indicated that obesity was reported to be associated with higher prostate cancer grade at diagnosis. However, it is difficult in human studies to adequately assess effects of body weight and/or the effects of body weight change at specific ages on prostate cancer given the long life span. Recent introduction of the TRAMP (transgenic adenocarcinoma mouse prostate) mouse provides a model that shares many characteristics with human prostate cancer. The initial goal of this proposal was to determine the effect of obesity induced at different ages on the development of prostate cancer in TRAMP mice. Obesity was induced by injections with gold-thioglucose (GTG) at either 6, 16 or 26 weeks of age. Body weight was monitored and the mice were followed until 46 weeks of age. Unfortunately, there was an unexpectedly high mortality rate in TRAMP mice in response to the GTG injections. This resulted in a limited number of mice available to follow. However, the results we did obtain indicated little effect of obesity regardless of age of onset on prostate cancer development in this model. A second experiment was conducted using a prostate cancer cell line developed from a TRAMP mouse tumor, TRAMP-C2. Since this cell line was developed from a mouse on the C57BL6 background it can be inoculated into wild- type mice and tumor growth can then be monitored. C57BL6 male mice were fed a high fat diet and then divided by body weight into Obesity-Prone, Overweight and Obesity-Resistant groups with an additional group fed a low-fat diet. Mice were inoculated with the cell line and tumor growth followed. The high-fat diet per se affected tumor weight and size. Interestingly, genital-urinary and prostate weights were highest in the Obesity-Prone mice.