Expression, subcellular localization and phosphorylation status of annexins 1 and 5 in human pituitary adenomas and a growth hormone-secreting carcinoma

OBJECTIVE Annexin 1 (ANXA1), a 37-kDa protein, plays an important role as a mediator of glucocorticoid action in the anterior pituitary gland and has been implicated in the processes of tumorigenesis in a number of other tissues. As a prelude to examining the potential role of ANXA1 in the pathophysiology of pituitary tumours, this study examined the expression, phosphorylation status and distribution of ANXA1 and the closely related protein, annexin 5 (ANXA5), in a series of pituitary adenomas and in two carcinomas. PATIENTS AND DESIGN Forty-two human pituitary adenomas were examined. Parallel studies were performed on normal pituitary tissue, obtained postmortem, a GH-secreting carcinoma and a grade 4 astrocytoma. MEASUREMENTS The tissue was processed for analysis of ANXA1 mRNA and protein expression by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis and immunogold electron-microscopic histochemistry. Parallel measures of ANXA5 mRNA and protein were also made. RESULTS ANXA1 mRNA and protein were detected in all but three adenomas studied; the protein was localized mainly, but not exclusively, to nonendocrine cells. ANXA5 expression was more variable and was contained within both endocrine and nonendocrine cells of these tumours. In comparison with the adenomas, the GH-secreting carcinoma showed abundant expression of both ANXA1 and ANXA5, with intense ANXA1 staining in some but not all tumour/endocrine cells. A serine-phosphorylated species of ANXA1 was detected in all pituitary tumours studied; by contrast, tyrosine-phosphorylated ANXA1 was detected in only four adenomas and in the GH carcinoma. ANXA1 and ANXA5 were also expressed in abundance in the astrocytoma. CONCLUSIONS The results demonstrate expression of both ANXA1 and ANXA5 in human pituitary tumours and thus raise the possibility that these proteins influence the growth and/or functional activity of the tumours.