Tags

Type your tag names separated by a space and hit enter

Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line.
J Steroid Biochem Mol Biol. 2014 Jan; 139:7-15.JS

Abstract

Hedgehog (Hh)-signaling pathway is important in embryonic development. Activation of Hh-signaling is associated with tumorigenesis. Recent studies demonstrate that Hh-signaling is involved in the development of the adrenal gland in mice and is important in regulating adrenal proliferation. We studied the expression of Sonic hedgehog (SHH), Smoothened (SMO), Patched1 (PTCH1) and GLI family zinc finger 1 (GLI1) in human adrenal and in adrenocortical tumors using immunohistochemistry and semi-quantitative reverse transcriptase-polymerase chain reaction. Modulation of GLI1 and SMO messenger ribonucleic acid (mRNA) expression was investigated with forskolin. The role of Hh-signaling was studied in NCI-H295R cells and in an immortalized primary cell line using the Hh-agonist smoothened agonist (SAG) and the Hh-antagonist cyclopamine. The Hh-pathway components SHH, GLI1, PTCH1 and SMO were detectable in all adrenal glands. While in cortisol-producing adenomas (CPA), Hh-signaling expression levels were comparable to that in normal adrenal cortex, a much higher mRNA expression of GLI1, SMO and SHH was observed in non-producing adenomas (NPA). Interestingly, stimulation of cultured adrenal cells with forskolin led to a decrease in expression of GLI1 and SMO mRNAs. Antagonism of Hh-signaling resulted in a lower proliferation rate of adrenocortical cells, while Hh-agonism had no significant effect on adrenal cell proliferation. Our data show Hh-signaling activity in adult adrenal glands. Activation of the PKA pathway results in lower expression of Hh-signaling proteins. This might explain the lower expression of the Hh components GLI1 and SMO in CPA in comparison to the higher expression in NPA. Hh-signaling might be involved in the tumorigenesis of NPA.

Authors+Show Affiliations

Department of Endocrinology and Diabetology, Medical Faculty, University of Dusseldorf, D-40225 Duesseldorf, Germany; Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Medical Faculty, University of Dusseldorf, D-40225 Duesseldorf, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24063979

Citation

Werminghaus, Pascal, et al. "Hedgehog-signaling Is Upregulated in Non-producing Human Adrenal Adenomas and Antagonism of Hedgehog-signaling Inhibits Proliferation of NCI-H295R Cells and an Immortalized Primary Human Adrenal Cell Line." The Journal of Steroid Biochemistry and Molecular Biology, vol. 139, 2014, pp. 7-15.
Werminghaus P, Haase M, Hornsby PJ, et al. Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line. J Steroid Biochem Mol Biol. 2014;139:7-15.
Werminghaus, P., Haase, M., Hornsby, P. J., Schinner, S., Schott, M., Malendowicz, L. K., Lammers, B. J., Goretzki, P. E., Müller-Mattheis, V., Markus Giessing, ., & Willenberg, H. S. (2014). Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line. The Journal of Steroid Biochemistry and Molecular Biology, 139, 7-15. https://doi.org/10.1016/j.jsbmb.2013.09.007
Werminghaus P, et al. Hedgehog-signaling Is Upregulated in Non-producing Human Adrenal Adenomas and Antagonism of Hedgehog-signaling Inhibits Proliferation of NCI-H295R Cells and an Immortalized Primary Human Adrenal Cell Line. J Steroid Biochem Mol Biol. 2014;139:7-15. PubMed PMID: 24063979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line. AU - Werminghaus,Pascal, AU - Haase,Matthias, AU - Hornsby,Peter J, AU - Schinner,Sven, AU - Schott,Matthias, AU - Malendowicz,Ludwik K, AU - Lammers,Bernhard J, AU - Goretzki,Peter E, AU - Müller-Mattheis,Volker, AU - Markus Giessing,, AU - Willenberg,Holger S, Y1 - 2013/09/21/ PY - 2013/03/06/received PY - 2013/07/12/revised PY - 2013/09/12/accepted PY - 2013/9/26/entrez PY - 2013/9/26/pubmed PY - 2014/2/4/medline KW - Adrenal KW - GLI1 KW - Hedgehog KW - SHH KW - Tumor SP - 7 EP - 15 JF - The Journal of steroid biochemistry and molecular biology JO - J Steroid Biochem Mol Biol VL - 139 N2 - Hedgehog (Hh)-signaling pathway is important in embryonic development. Activation of Hh-signaling is associated with tumorigenesis. Recent studies demonstrate that Hh-signaling is involved in the development of the adrenal gland in mice and is important in regulating adrenal proliferation. We studied the expression of Sonic hedgehog (SHH), Smoothened (SMO), Patched1 (PTCH1) and GLI family zinc finger 1 (GLI1) in human adrenal and in adrenocortical tumors using immunohistochemistry and semi-quantitative reverse transcriptase-polymerase chain reaction. Modulation of GLI1 and SMO messenger ribonucleic acid (mRNA) expression was investigated with forskolin. The role of Hh-signaling was studied in NCI-H295R cells and in an immortalized primary cell line using the Hh-agonist smoothened agonist (SAG) and the Hh-antagonist cyclopamine. The Hh-pathway components SHH, GLI1, PTCH1 and SMO were detectable in all adrenal glands. While in cortisol-producing adenomas (CPA), Hh-signaling expression levels were comparable to that in normal adrenal cortex, a much higher mRNA expression of GLI1, SMO and SHH was observed in non-producing adenomas (NPA). Interestingly, stimulation of cultured adrenal cells with forskolin led to a decrease in expression of GLI1 and SMO mRNAs. Antagonism of Hh-signaling resulted in a lower proliferation rate of adrenocortical cells, while Hh-agonism had no significant effect on adrenal cell proliferation. Our data show Hh-signaling activity in adult adrenal glands. Activation of the PKA pathway results in lower expression of Hh-signaling proteins. This might explain the lower expression of the Hh components GLI1 and SMO in CPA in comparison to the higher expression in NPA. Hh-signaling might be involved in the tumorigenesis of NPA. SN - 1879-1220 UR - https://www.unboundmedicine.com/medline/citation/24063979/Hedgehog_signaling_is_upregulated_in_non_producing_human_adrenal_adenomas_and_antagonism_of_hedgehog_signaling_inhibits_proliferation_of_NCI_H295R_cells_and_an_immortalized_primary_human_adrenal_cell_line_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-0760(13)00181-7 DB - PRIME DP - Unbound Medicine ER -