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Published on: October 2, 2018
Control of the adrenocortical cell cycle: interaction between FGF2 and ACTH
1Departamento de Bioquímica, Universidade de São Paulo, Brasil.
Abstract:
FGF2 elicits a strong mitogenic response in the mouse Y-1 adrenocortical tumor cell line, that includes a rapid and transient activation of the ERK-MAPK cascade and induction of the c-Fos protein. ACTH, itself a very weak mitogen, blocks the mitogenic response effect of FGF2 in the early and middle G1 phase, keeping both ERK-MAPK activation and c-Fos induction at maximal levels. Probing the mitogenic response of Y-1 cells to FGF2 with ACTH is likely to uncover reactions underlying the effects of this hormone on adrenocortical cell growth.
Insights
Fibroblast Growth Factor 2 (FGF2) strongly stimulates Y-1 cell growth by activating ERK-MAPK and c-Fos. Adrenocorticotropic Hormone (ACTH) blocks this FGF2 effect, revealing insights into adrenocortical cell regulation.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Fibroblast Growth Factor 2 (FGF2) is a potent mitogen for mouse Y-1 adrenocortical tumor cells.
- This mitogenic response involves the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) cascade and c-Fos protein induction.
- Adrenocorticotropic Hormone (ACTH) is a weak mitogen but can modulate cellular responses.
Purpose of the Study:
- To investigate the interaction between FGF2 and ACTH in regulating Y-1 cell proliferation.
- To elucidate the molecular mechanisms underlying ACTH's modulation of FGF2-induced mitogenesis.
- To uncover signaling pathways involved in adrenocortical cell growth regulation.
Main Methods:
- Utilized mouse Y-1 adrenocortical tumor cell line.
- Stimulated cells with FGF2 and ACTH, individually and in combination.
- Monitored ERK-MAPK cascade activation and c-Fos protein induction.
- Assessed cell proliferation and cell cycle progression.
Main Results:
- FGF2 induced rapid and transient ERK-MAPK activation and c-Fos expression in Y-1 cells.
- ACTH, a weak mitogen, inhibited the mitogenic effects of FGF2.
- ACTH maintained maximal ERK-MAPK activation and c-Fos induction despite blocking FGF2's mitogenic effect.
- ACTH interfered with FGF2's mitogenic action during early and mid-G1 phase.
Conclusions:
- ACTH antagonizes FGF2-driven proliferation in Y-1 cells by modulating specific cell cycle phases.
- The interplay between FGF2 and ACTH signaling provides insights into the complex regulation of adrenocortical cell growth.
- Understanding these interactions is crucial for comprehending normal and pathological adrenocortical function.
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