Cell Growth & Differentiation, Vol 6, Issue 1 91-95, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Ki-ras oncogene interferes with the expression of cyclic AMP-dependent promoters

A Gallo, A Feliciello, A Varrone, R Cerillo, ME Gottesman and VE Avvedimento
Dipartimento di Biologia e Patologia Molecolare e Cellulare, II Facolta di Medicina e Chirurgia, Universita di Napoli Federico II, Italy.

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.

This article has been cited by other articles:

				M. G. Baratta, I. Porreca, and R. Di Lauro Oncogenic Ras Blocks the cAMP Pathway and Dedifferentiates Thyroid Cells Via an Impairment of Pax8 Transcriptional Activity Mol. Endocrinol., June 1, 2009; 23(6): 838 - 848. [Abstract] [Full Text] [PDF]

				L. Casalino, D. De Cesare, and P. Verde Accumulation of Fra-1 in ras-Transformed Cells Depends on Both Transcriptional Autoregulation and MEK-Dependent Posttranslational Stabilization Mol. Cell. Biol., June 15, 2003; 23(12): 4401 - 4415. [Abstract] [Full Text] [PDF]

				F. M. Torti and S. V. Torti Regulation of ferritin genes and protein Blood, May 15, 2002; 99(10): 3505 - 3516. [Full Text] [PDF]

				D. L. Medina, M. Rivas, P. Cruz, I. Barroso, J. Regadera, and P. Santisteban RhoA Activation Promotes Transformation and Loss of Thyroid Cell Differentiation Interfering with Thyroid Transcription Factor-1 Activity Mol. Endocrinol., January 1, 2002; 16(1): 33 - 44. [Abstract] [Full Text] [PDF]

				S. Umar, J. H. Sellin, and A. P. Morris Murine colonic mucosa hyperproliferation. II. PKC-beta activation and cPKC-mediated cellular CFTR overexpression Am J Physiol Gastrointest Liver Physiol, May 1, 2000; 278(5): G765 - G774. [Abstract] [Full Text] [PDF]

				N. Fernandez, M. J. Caloca, G. V. Prendergast, J. L. Meinkoth, and M. G. Kazanietz Atypical Protein Kinase C-{zeta} Stimulates Thyrotropin-Independent Proliferation in Rat Thyroid Cells Endocrinology, January 1, 2000; 141(1): 146 - 152. [Abstract] [Full Text] [PDF]

				P. Nelson, K Moissoglu, J Vargas, P. Klotman, and I. Gelman Involvement of the protein kinase C substrate, SSeCKS, in the actin-based stellate morphology of mesangial cells J. Cell Sci., January 2, 1999; 112(3): 361 - 370. [Abstract] [PDF]

				M. A. Bevilacqua, M. C. Faniello, B. Quaresima, M. T. Tiano, P. Giuliano, A. Feliciello, V. E. Avvedimento, F. Cimino, and F. Costanzo A Common Mechanism Underlying the E1A Repression and the cAMP Stimulation of the H Ferritin Transcription J. Biol. Chem., August 15, 1997; 272(33): 20736 - 20741. [Abstract] [Full Text] [PDF]

				A. Feliciello, P. Giuliano, A. Porcellini, C. Garbi, S. Obici, E. Mele, E. Angotti, D. Grieco, G. Amabile, S. Cassano, et al. The v-Ki-Ras Oncogene Alters cAMP Nuclear Signaling by Regulating the Location and the Expression of cAMP-dependent Protein Kinase IIbeta J. Biol. Chem., October 11, 1996; 271(41): 25350 - 25359. [Abstract] [Full Text] [PDF]