? ? This pilot application is to determine the effects of parental metabolic status on the onset of cancer in the offspring. Specifically, we propose that parental metabolic syndrome (MS) increases the development of breast cancer in female offspring and the development of prostate cancer in male offspring. The prevalence of MS is high and increasing in parallel with increasing incidences of certain types of cancer, such as breast and prostate cancers, suggesting that MS may be an important etiological factor for breast and prostate cancers. Accumulating evidence from epidemiological investigations and experimental studies has suggested that predisposition to the MS may also be acquired very early in development through inappropriate fetal or neonatal nutrition via altered maternal dietary intake. It is thus possible that parental, especially maternal MS may disturb metabolic programming of the offspring during intrauterine development, resulting in increased risks of MS and subsequent cancer in the offspring. However, very limited experimental research has been done to investigate the inter-relationships between parental MS and cancer risks of their offspring. This pilot application is to generate critical experimental evidence for testing our hypothesis that parental MS increases the risk of breast cancer in female offspring and the risk of prostate cancer in male offspring. We propose to apply a relevant C3(1)/SV40 Tag transgenic mouse model for the proposed studies. Female transgenic mouse develops mammary tumor and male transgenic mouse develops prostate tumor.
Specific Aim 1 is to determine the effects of parental MS on the development of mammary tumor in female offspring and prostate tumor in male offspring. The wild-type female FVB mice and male C3(1)/SV40 Tag transgenic male mice will be fed either a control diet or a high fat/high refined sugar (HF/HS) diet. The transgenic female and male offspring will be monitored for the development of mammary tumor and prostate tumor, respectively.
Specific Aim 2 is to further determine the related biomarkers that are associated with the stimulatory effect of the parental MS on the development of breast and prostate cancers in the female and male offspring, respectively. We will first determine a series of metabolic biomarkers in the parents and in the female and male offspring (Aim 2A). In addition, cDNA microarray assays will be performed to identify potential molecular targets that may provide new insights into the molecular mechanisms by which the parental MS stimulates the development of breast and prostate cancers in female and male offspring, respectively (Aim 2B). The proposed studies will provide direct supporting evidence to support or against the causal roles of parental MS in the development of breast cancer in female offspring and/or prostate cancer in male offspring. It will provide critically important evidence to support the cancer prevention strategy by alleviating metabolic disorders in the parents. The results also provide essential supporting preliminary data for future RO1 grant application investigate effective dietary or nutritional regimens for cancer prevention by targeting parental MS. ? ? ?
