Cocaine and amphetamine regulated transcript (CART): a newly characterized neuropeptide in human prostate

Biotech Histochem. 2023 Nov;98(7):508-522. doi: 10.1080/10520295.2023.2245328. Epub 2023 Aug 24.

Abstract

Cocaine and amphetamine regulated transcript (CART) is a somatostatin-like polypeptide. CART has been localized in the CNS, hypothalamo-pituitary-adrenocortical (HPA) axis, pancreatic islets and enteric nervous system. We investigated the cellular localization of CART in normal human prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia and acinar adenocarcinoma. CART was assessed using immunohistochemistry (IHC) and in situ hybridization (ISH), and its gene expression was identified by RTqPCR. We found cellular expression of CART in both normal prostatic luminal secretory epithelial cells neuroendocrine cells (NEC) of both ducts and acini. The cellular appearance indicated a cycle of neuropeptide synthesis and secretion as validated by ISH/IHC concordance. RTqPCR analysis also validated the immunohistochemical data and gene expression, which both indicated low to moderate expression in prostatic tissues. CART expression also was increased in both neuroendocrine and glandular epithelial cell populations from samples of benign prostatic hyperplasia as validated by IHC, ISH and RTqPCR. CART expression was markedly diminished and, in some cases, entirely absent in tissues of prostatic intraepithelial neoplasia and adenocarcinoma. Owing to loss of CART expression in adenocarcinoma and its increase in benign prostatic hyperplasia, CART may prove to be an important prostate marker.

Keywords: Amphetamine; CART; cocaine; human; neuropeptide; prostate; prostatic epithelium.

MeSH terms

  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / pathology
  • Humans
  • Male
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Hyperplasia* / genetics
  • Prostatic Hyperplasia* / metabolism
  • Prostatic Hyperplasia* / pathology
  • Prostatic Intraepithelial Neoplasia* / metabolism
  • Prostatic Intraepithelial Neoplasia* / pathology
  • Prostatic Neoplasms* / metabolism

Substances

  • cocaine- and amphetamine-regulated transcript protein