Year: 2007
Type: dissertation
Abstract: Chromaffin cells are a modified post-ganglionic sympathetic neuron, which synthesise and secrete catecholamines.The neoplastic transformation of chromaffin cells is demonstrated by the tumour phaeochromocytoma, a functional tumour that recapitulates the normal role of chromaffin cells by synthesising, storing and releasing excess catecholamines.Within this thesis we have explored several aspects of chromaffin cell and phaeochromocytoma tumour biology, including the specific expression of key sympathoadrenal markers such as the noradrenaline transporter (NAT), neuropeptide Y (NPY) and chromogranin A (CGA) in normal human and mouse chromaffin cells versus phaeochromocytomas of human and mouse origin.Catecholamine-mediated signalling in chromaffin cells is terminated by the sequestration of extracellular catecholamines back into the cell via the noradrenaline transporter (NAT).Following observations that within the rat adrenal medulla, NAT is expressed in PNMT-positive chromaffin cells we explored whether this pattern of expression is also present in the human adrenal medulla.While we successfully established that NAT and PNMT are co-localised, we also found that all human adrenal chromaffin cells are PNMT-positive.In the rat, NAT is also observed within the cytoplasm and has been suggested to be associated with secretory vesicles, thus using the secretory vesicle marker, CGA, we demonstrate that NAT is associated with secretory vesicles.However, in contrast to our findings within the normal chromaffin cells, in situ NAT expression in human phaeochromocytoma tumour samples was distorted, with observed changes including the level and type of staining observed, and disruptions to the strict NAT-CGA association observed in the normal adrenal.Continuing our theme of NAT, we investigated if pre-treating the phaeochromocytoma PC12 cell line with the chemotherapy drug cisplatin had an effect on the expression of NAT, to give an indication of the efficacy of this compound in the
Author: Susannah Cleary
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1509699758