Expression of PDE11A in Normal and Malignant Human Tissues

Abstract

S U M M A R Y Cyclic nucleotide phosphodiesterase 11A (PDE11A) is the newest member in the PDE family. Although the tissue distribution of PDE11A mRNA has been shown, its protein expression pattern has not been well studied. The goal of this report is to investigate the distribution of PDE11A proteins in a wide range of normal and malignant human tissues. We utilized a polyclonal antibody that recognized all four PDE11A isoforms. Its specificity was demonstrated by Western blot analysis on a recombinant human PDE11A protein and native PDE11A proteins in various human tissues. Immunohistochemistry showed that PDE11A is widely expressed. Various degrees of immunoreactivity were observed in the epithelial cells, endothelial cells, and smooth muscle cells of all tissues examined. The highest expression was in the epithelial, endothelial, and smooth muscle cells of the prostate, Leydig, and spermatogenic cells of the testis, the tubule epithelial cells in the kidney, the epithelial and endothelial cells in the adrenal, the epithelial cells and macrophages in the colon, and the epidermis in the skin. Furthermore, PDE11A expression was also detected in several human carcinomas. Our results suggest that PDE11A might be involved in multiple physiological processes in various organs via its ability to modulate intracellular cAMP and cGMP levels.

Adrenal Hyperplasia and Adenomas Are Associated with Inhibition of Phosphodiesterase 11A in Carriers of PDE11A Sequence Variants That Are Frequent in the Population

“…Recently, after running a wholegenome association study, we reported inactivating mutations of the phosphodiesterase 11A (PDE11A) in a subgroup of patients with primary pigmented nodular adrenocortical disease and other forms of bilateral hyperplasia (7). PDE11A is a dual-specificity phosphodiesterase; it is expressed in several endocrine tissues, including the adrenal cortex (8)(9)(10)(11)(12). The PDE11A gene was mapped to the 2q31-35 chromosomal region and the adrenal tumors from patients with PDE11A-inactivating mutations showed 2q allelic losses, although a cause-and-effect relationship could not be shown because the study was a loss-of-heterozygosity and association one (7).…”

Phosphodiesterase 11A in brain is enriched in ventral hippocampus and deletion causes psychiatric disease-related phenotypes

“…With respect to the brain, initial studies failed to identify PDE11A mRNA in samples from an entire brain or whole brain regions (3,4). This failure is not surprising, given that a later study employing immunohistochemistry reported sporadic, low levels of expression in "neurons" and "glia" [brain region not identified (11)]. If PDE11A is expressed only in a subpopulation of cells within a discrete subregion of the brain, one might not expect to detect expression when analyzing samples prepared from an entire brain (region).…”

Endothelial Lipase Is Localized to Follicular Epithelial Cells in the Thyroid Gland and Is Moderately Expressed in Adipocytes

“…Slides were deparaffinized, hydrated, and processed for routine IHC as previously described (D'Andrea et al 2005;D'Andrea et al 2000). Briefly, slides were microwaved in Target buffer (Dako, Carpinteria, CA), cooled, placed in distilled H 2 O, and then treated with 3.0% H 2 O 2 for 10 min.…”