The impact of diet and micronutrient supplements on the expression of neuroendocrine markers in murine Lady transgenic prostate.
BACKGROUND
Neuroendocrine (NE) differentiation (NED) in prostate cancer (PCa) is associated with morbidity and death; however, the underlying cause(s) promoting NED in PCa have yet to be determined. In this study, we examined the effect of both diet and micronutrient supplementation on the expression of NE markers using the Lady (12T-10) transgenic model of PCa. Lady (12T-10) transgenic animals develop advanced adenocarcinoma with NE characteristics that exhibits metastases in approximately 80% of cases. In this model a high fat diet has been shown to increase the severity of disease, while the use of micronutrients can inhibit this progression.


METHODS
In this study we used immunohistochemical analysis to determine expression of the NE markers: chromogranin A (CgA), neuron-specific enolase (NSE), bombesin, parathyroid hormone-related peptide (PTHrP), neurotensin and serotonin in prostates of PCa-bearing Lady (12T-10) mice.


RESULTS
High fat diet was correlated with significantly elevated expression of CgA and serotonin in prostate tissue of Lady (12T-10) mice. Addition of micronutrients to the control and high fat diet reproducibly elevated PTHrP and bombesin expression and suppressed NSE expression, while prostate tissue from the control diet supplemented with micronutrients exhibited significantly lower numbers of calcitonin- and neurotensin-positive cells.


CONCLUSIONS
These results highlight the importance of dietary control in management of disease and identify differential changes in NE marker expression, which may be diagnostically viable in monitoring the impact of therapies on disease status.
Palmer
Jodie
J
The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada.
Venkateswaran
Vasundara
V
Fleshner
Neil E
NE
Klotz
Laurence H
LH
Cox
Michael E
ME
D000230:Adenocarcinoma / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D000821:Animal Feed; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001839:Bombesin / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D053379:Chromogranin A / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018977:Micronutrients / Q000494:pharmacology*; D009496:Neurotensin / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000378:metabolism
D015415:Biomarkers; D053379:Chromogranin A; D004041:Dietary Fats; D018977:Micronutrients; D044162:Parathyroid Hormone-Related Protein; D012701:Serotonin; D009496:Neurotensin; D010751:Phosphopyruvate Hydratase; D001839:Bombesin