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- Backlin, Carin, et al.
(författare)
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Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex
- 1995
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 15:6B, s. 2453-2459
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion.MATERIAL AND METHODS:Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation.RESULTS:Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody.CONCLUSION:IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.
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- Carling, Tobias, et al.
(författare)
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Hyperparathyroidism of multiple endocrine neoplasia type 1 : candidate gene and parathyroid calcium sensing protein expression
- 1995
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 118:6, s. 924-931
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression and function of a putative calcium sensing protein (CAS) in hyperparathyroidism of MEN 1.METHODS:In 31 parathyroid glands from 17 patients with MEN 1, CAS distribution was studied immunohistochemically and parallel sections were explored for PLC beta 3 mRNA expression by in situ hybridization. Enzymatically dispersed parathyroid cells were analyzed for cytoplasmic calcium concentrations [Ca2+]i and parathyroid hormone (PTH) release.RESULTS:All glands exhibited a heterogeneously reduced CAS immunoreactivity, especially meager in nodularly assembled parathyroid cells. Calcium regulated [Ca2+]i and PTH release tended to be more deranged in the glands possessing the lowest immunostaining. Parathyroid PLC beta 3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC beta 3 expression in endocrine pancreatic tumors.CONCLUSIONS:The findings support variable calcium insensitivity of [Ca2+]i and PTH release in hyperparathyroidism of MEN 1, apparently coupled to heterogeneously reduced CAS expression. For clarification of the role of PLC beta 3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.
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- Carling, Tobias, et al.
(författare)
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Parathyroid MEN 1 gene mutations in relation to clinical characteristics of non-familial primary hyperparathyroidism
- 1998
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:8, s. 2960-2963
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Tidskriftsartikel (refereegranskat)abstract
- Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.
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