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β-Catenin activation and illicit receptor expression in adrenocortical cells

Abstract : Adrenal cortisol-producing tumors can express illicit membrane receptors such as luteinizing hormone (LH), glucose-dependent insulinotropic peptide (GIP) or type 4 and 7 serotonin (5-HT 4/7 ) receptors. Abnormal expression of the LH receptor (LH-R) has been ascribed to the activation of the Wnt/β-catenin signaling pathway in adrenocortical cells. In the present study, we have investigated whether β-catenin activation may also trigger the illegitimate expression of GIP and 5-HT receptors. Three models of β-catenin activation in adrenocortical cells were used: an APC -mutated adrenocortical tumor, human-transfected adrenocortical cells and genetically modified mouse adrenal glands. The methods employed include quantitative reverse transcription PCR, immunohistochemistry and measurement of cortisol secretion by cultured tumor cells. Abnormal expression of the GIP, 5-HT 7 and LH receptors was observed in the APC -mutated adrenocortical tumor tissue. In addition, GIP, 5-HT and human chorionic gonadotropin stimulated cortisol production from tumor cells in primary culture. Conversely, only the LHCGR was upregulated in human and mouse adrenocortical cells harboring the activation of β-catenin. Moreover, LH-R immunoreactivity was detected in clusters of zona fasciculata cells in the β-catenin-activated mouse model. Our data indicate that activation of the β-catenin signaling pathway can promote the illicit expression of functional LH-Rs in adrenal zona fasciculata cells but does not favor the abnormal expression of GIP and 5-HT receptors.
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Contributor : Pierre Val Connect in order to contact the contributor
Submitted on : Tuesday, November 22, 2022 - 8:18:37 AM
Last modification on : Wednesday, November 23, 2022 - 3:31:12 AM




Julie Le Mestre, Michaël Thomas, Céline Duparc, Pierre Val, Clémence Bures, et al.. β-Catenin activation and illicit receptor expression in adrenocortical cells. Endocrine-Related Cancer, 2022, 29 (3), pp.151-162. ⟨10.1530/ERC-21-0298⟩. ⟨hal-03864819⟩



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