Signaling pathways in adrenocortical cancer.
Adrenocortical carcinoma is a rare tumor that carries a very poor prognosis. Despite efforts to develop new therapeutic regimens to treat this disease, surgery remains the mainstay of treatment. Laboratory studies of adrenocortical cancers have revealed a wide variety of signaling pathways that can be altered in these neoplasms. Although ACTH signaling through adenylyl cyclase and protein kinase A is important for normal adrenal cellular physiology, there is evidence to suggest that this pathway may inhibit the growth of adrenocortical tumors, and that inactivation of the ACTH receptor may promote tumor formation. Although multiple signal transduction pathways are essential for normal adrenal growth and hormone secretion, efforts to identify events required for neoplastic transformation have met with limited success. Alterations that have frequently been observed in adrenocortical carcinoma include up-regulation of the IGF-II system, as well as mutations in TP53 and RAS. Current studies aim to elucidate the mechanisms of tumor growth by studying proproliferative signaling pathways, such as those involving Akt/PKB and the mitogen-activated protein kinases (MAPKs). Although studies of single pathways have been helpful in guiding investigations, new tools to study the integration and multiplicity of signaling pathways hold the hope of improved understanding of the signaling pathway alterations in adrenocortical cancer.
Unit on Genetics and Endocrinology, DEB, NICHD, National Instutes of Health, Bethesda, Maryland 20892-1862, USA.
Lawrence S
LS
Kirschner
D000306:Adrenal Cortex Neoplasms / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D011956:Receptors, Cell Surface; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases