title: Ki-ras oncogene interferes with the expression of cyclic AMP-dependent promoters.
abstract: The expression of thyroglobulin and other thyroid-specific markers depends upon the activation of protein kinase A (PKA) by cyclic AMP. A rat thyroid cell line dedifferentiates when transformed with Ki-ras oncogene. The decrease in thyroglobulin gene expression parallels a reduction in the level of PKA nuclear catalytic subunit. We find that the activity of cAMP-responsive elements and thyroglobulin promoters is down-regulated in Ras-transformed cells. Transcription of a third cAMP-regulated gene, H-ferritin, is similarly reduced. cAMP-responsive element and H-ferritin expression were stimulated when intracellular cAMP levels were increased. Reactivation of the thyroglobulin promoter required depletion of PKC in addition to increased cAMP. We also find that v-Ras activation leads to a significant increase in membrane-bound PKC. These data support the idea that v-Ras via PKC inhibits the transmission of cAMP-PKA signals to the nucleus. We suggest that the thyroglobulin promoter is more sensitive than other cAMP-dependent promoters to reduced nuclear levels of PKA catalytic subunit.
authors.affiliation: Dipartimento di Biologia e Patologia Molecolare e Cellulare, II Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gallo
authors.forename: A
authors.initials: A
authors.lastname: Feliciello
authors.forename: A
authors.initials: A
authors.lastname: Varrone
authors.forename: R
authors.initials: R
authors.lastname: Cerillo
authors.forename: M E
authors.initials: ME
authors.lastname: Gottesman
authors.forename: V E
authors.initials: VE
authors.lastname: Avvedimento
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005293:Ferritins / Q000235:genetics; D005786:Gene Expression Regulation; D011905:Genes, ras; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D014162:Transfection / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D005293:Ferritins; D013954:Thyroglobulin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C