An Immortalized Human Cell Line Bearing a PRKAR1A-Inactivating Mutation: Effects of Overexpression of the Wild-Type Allele and Other Protein Kinase A Subunits

Abstract

This is the first immortalized cell line with a naturally occurring PRKAR1A-inactivating mutation that is associated in vivo with tumor formation. PKA isozyme balance is critical for the control of cAMP signaling and related cell cycle and proliferation changes. Finally, E2F1 may be a factor that mediates dysregulated PKA's effects on the cell cycle.

Increased Protein Kinase A Activity in the Prkar1a-defective Mouse is Associated with Hyperarousal and Increased Anxiety

“…In accord with prior studies, results of our experiment provide support for the role of androgens in attenuation of the stress reactivity of adult males (27,28,35,39,40,43,(47)(48)(49)52).…”

Comparison of Aldosterone Production Among Human Adrenocortical Cell Lines

“…Currently, the most widely utilized model system is the cell lines developed from the human adrenocortical tumors [18–21]. The list of such permanent cell lines is remarkably short, consisting of the CAR47 [22], SW13 [23], NCI-H295 [24] and its substrains: H295A [25] and H295R [20]. However, a side-by-side comparison of these cell lines has not been described.…”

PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease

“…The immortalized adrenocortical CAR47 cell line, derived from a patient with PPNAD, was cultured under the normal growth conditions previously described (32). Cells were incubated 6 hours and 12 hours with forskolin (10 -5 M; Sigma-Aldrich) or H-89 (10 -5 M) to investigate expression of mRNAs and proteins.…”

“…We have investigated the regulation of 5-HTR expression in PPNAD by using the PRKAR1A-mutated PPNAD CAR47 cell line (32), which expressed HTR4 and HTR7 mRNAs but not the HTR6 mRNA (Figure 4, A Inhibition of PRKAR1A expression triggers expression of a serotonergic loop in the human adrenocortical cell line H295R. Previous investigations have shown that PRKAR1A silencing increases total PKA activity in adrenocortical H295R cell lines (33), as observed in PPNAD cells.…”