Related Experiment Video

Updated: Aug 16, 2026

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
08:11

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

Published on: March 26, 2018

cAMP pathway alterations from the cell surface to the nucleus in adrenocortical tumors

Dan Rosenberg1, Lionel Groussin, Xavier Bertagna

  • 1Département d'Endocrinologie, INSERM U 567, CNRS UMR 8104, IFR 116, Institut Cochin, 24 rue du Fg-St-Jacques, 75014, Paris, France.

Endocrine Research
|January 18, 2003
PubMed

Insights

The cyclic AMP (cAMP) pathway is crucial in endocrine tumors. Defects in cAMP signaling components, like G protein-coupled receptors and protein kinase A, are linked to adrenal tumors and Cushing's syndrome.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • The cyclic AMP (cAMP) pathway is vital for endocrine tissue development.
  • Molecular defects in cAMP pathway components are implicated in endocrine tumors.
  • Adrenocorticotropin hormone (ACTH) activates the cAMP pathway in the adrenal cortex, and its hypersecretion causes Cushing's syndrome.

Purpose of the Study:

  • To investigate the role of the cAMP pathway in adrenocortical tumorigenesis.
  • To examine the expression and alterations of key cAMP pathway components in various adrenal tumors.
  • To understand the molecular mechanisms underlying ACTH-independent Cushing's syndrome (ACS).

Main Methods:

  • Screening for abnormal responses in patients with ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH).
  • Analyzing somatic and germ line mutations in PRKAR1.
  • Evaluating the expression of cyclic AMP response element binding protein (CREB) and related proteins in adrenal cancer cell lines and tumors.

Main Results:

  • Ectopic expression of the gastric inhibitory peptide receptor (GIP-R) is frequent in AIMAH, rare in adrenal adenoma (AA), and absent in adrenal cancer (AC).
  • Nearly all AIMAH patients showed abnormal cortisol responses, suggesting "illegitimate" receptor expression.
  • Inactivating mutations of PRKAR1 were observed in patients with primary pigmented nodular adrenocortical disease (PPNAD) and AA causing ACS.
  • Alterations in CREB family proteins, including loss of CREB and compensatory overexpression of CREMtau, were found in human adrenocortical cancer cell lines and tumors.

Conclusions:

  • Various alterations in the cAMP signaling pathway, leading to either activation or inactivation of its components, are involved in adrenocortical tumorigenesis.
  • The study highlights the significance of cAMP pathway dysregulation in the development of adrenal tumors and associated hormonal imbalances.
  • Specific molecular defects, such as abnormal GIP-R expression and alterations in CREB signaling, contribute to the pathogenesis of conditions like ACS and adrenocortical cancer.

More Related Videos

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions04:33

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions

Published on: March 12, 2019

Establishment of Zone-Enriched Primary Cultures from the Mouse Adrenal Cortex07:43

Establishment of Zone-Enriched Primary Cultures from the Mouse Adrenal Cortex

Published on: May 8, 2026

Related Concept Videos

Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...