cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

Jiangi Liu, Xiao-Dong Li, A. Ora, P. Heikkilä, A. Vaheri, R. Voutilainen

Research output: Contribution to journalArticle

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Abstract

Adrenocorticotropin is the major regulator of adrenocortical development and function. It acts mainly through the cAMP-dependent protein kinase A (PKA) pathway. Our aim was to study the interaction of tumor necrosis factor-α (TNFα) and the PKA pathway in adrenocortical cell proliferation and apoptosis. The PKA activator Dibutyryl cAMP ((Bu)2cAMP) strongly induced differentiation and inhibited proliferation in the human adrenocortical cell line NCI-H295R (H295R). TNFα induced apoptosis of H295R cells. Interestingly, (Bu)2cAMP treatment clearly enhanced TNFα -induced apoptosis in H295R cells, but not in another human adrenocortical cell line SW-13, the mouse adrenocortical Y-1 cell line or the human HeLa cell line. This synergistic effect was not due to the (BU)2cAMP-induced glucocorticoid secretion since dexamethasone had no significant effect on the TNFα-induced apoptosis. (Bu)2cAMP treatment rapidly increased the expression of the proto-oncogene c-myc in H295R cells, but not in SW-13, Y-1 or HeLa cells. In transient c-myc transfection assay, c-myc expression associated with decreased expression of the proliferation marker Ki-67 in H295R cells. In conclusion, cAMP-dependent protein kinase activation reduced proliferation and augmented TNFα-induced apoptosis in adrenocortical H295R cells, and these effects were associated with increased c-myc expression.

Original languageEnglish (US)
Pages (from-to)511-522
Number of pages12
JournalJournal of Molecular Endocrinology
Volume33
Issue number2
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Cyclic AMP-Dependent Protein Kinases
Tumor Necrosis Factor-alpha
Apoptosis
Cell Line
HeLa Cells
myc Genes
Adrenocorticotropic Hormone
Dexamethasone
Glucocorticoids
Transfection
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells. / Liu, Jiangi; Li, Xiao-Dong; Ora, A.; Heikkilä, P.; Vaheri, A.; Voutilainen, R.

In: Journal of Molecular Endocrinology, Vol. 33, No. 2, 01.10.2004, p. 511-522.

Research output: Contribution to journalArticle

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