Bone morphogenetic proteins 2 and 5 are down-regulated in adrenocortical carcinoma and modulate adrenal cell

Inga K Johnsen1, Roland Kappler, Christoph J Auernhammer

  • 1Departments of Medicine, University Hospital Innenstadt, Ludwig Maximilians University, Munich, Germany.

Cancer Research
|July 9, 2009
PubMed

Insights

Loss of Bone Morphogenetic Proteins (BMP) expression is common in adrenocortical tumors. BMP signaling inhibits tumor cell growth and steroidogenesis, suggesting a role in adrenocortical cancer.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Bone morphogenetic proteins (BMP) play a role in tumorigenesis across various cancers.
  • Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited therapeutic options.

Purpose of the Study:

  • To investigate the role of BMP signaling in adrenocortical tumors.
  • To determine the impact of BMPs on ACC cell proliferation, viability, and steroidogenic function.

Main Methods:

  • Quantitative PCR to assess BMP2 and BMP5 expression in tumor tissues and cell lines.
  • Smad1/5/8 pathway activation assays.
  • Cell proliferation and viability assays following BMP treatment.
  • Western blotting to analyze AKT phosphorylation.
  • Assessment of steroidogenic gene expression.
  • In vitro demethylation and GATA6 overexpression experiments.

Main Results:

  • Down-regulation of BMP2 and BMP5 observed in ACC tissues and cell lines compared to normal adrenal glands.
  • BMP treatment activated the Smad1/5/8 pathway and inhibited proliferation and viability.
  • BMPs reduced AKT phosphorylation and suppressed steroidogenic function.
  • Demethylation and GATA6 overexpression reactivated BMP pathways and modulated steroidogenesis.

Conclusions:

  • Loss of BMP ligand expression is frequent in adrenocortical tumors.
  • BMP-dependent pathways are implicated in regulating the malignant and functional phenotype of ACC cells.
  • BMP signaling represents a potential therapeutic target for adrenocortical cancer.

Related Concept Videos

Cushing Syndrome II: Pathophysiology01:19

Cushing Syndrome II: Pathophysiology

Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...
Hormones of the Adrenal Glands01:31

Hormones of the Adrenal Glands

Adrenal hormones play a pivotal role in maintaining the body's electrolyte balance and orchestrating responses to stress, showcasing the intricate functions of the adrenal cortex and medulla.
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and corticosterone...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Adrenal Gland Disorders01:27

Adrenal Gland Disorders

Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...