Identification of genes differentially expressed between a somatotrope and a lactotrope pituitary cell lines by representational difference analysis

Abstract

The molecular and cellular processes leading to the development and differentiation of the anterior pituitary gland is well characterized both in rodents and in human and rely on the highly regulated expression of transcription and growth factors. Yet regulatory mechanisms and signature molecules implicated in postnatal pituitary homeostasis, cell activation in physiological conditions and uncontrolled cell proliferation leading to pituitary tumorigenesis are still evasive and mediators of these events are still missing. To address this issue, representational difference analysis was applied to two established tumoral rodent cell lines, the GC cells secreting growth hormone and the 235-1 cells producing prolactin. A limited number of genes were expressed in only one cell line and not in the other. Several genes implicated in cell fate determination (Mb21d2, Gpc4, Creg1 and Wls) were identified. Their function in somatotrope or lactotrope cell specification remains to be determined. Half of the genes detected by RDA are potential candidate genes for pituitary tumorigenesis as they are implicated in signaling pathways associated with cell proliferation, oncogenic or tumor-suppressor function, epithelial to mesemchymal transition or invasiveness. These poorly characterized genes may encode new biomarkers relevant to the understanding of the molecular mechanisms associated with the development, proliferation or invasiveness of pituitary adenomas. The specific role of these new genes in the context of pituitary cell homeostasis or tumorigenesis will required further investigation as some of the identified genes were not reported to be associated with pituitary function in normal or pathological condition. The present work identified new genes encoding potential biomarkers that could turned out to be key intrinsic factors in pituitary tumorigenesis and molecular therapeutic targets in the treatment of human pituitary adenomas.