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Updated: Jun 23, 2026

Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells
Published on: February 18, 2016
Expression of p18(INK4C) is down-regulated in human pituitary adenomas
M Golam Hossain1, Takeo Iwata, Noriko Mizusawa
1Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Abstract:
Cyclin-dependent kinase inhibitors represented by the INK4 family comprising p16(INK4A), p15(INK4B), p18(INK4C), and p19(INK4D) are regulators of the cell cycle shown to be aberrant in many types of cancer. Mice lacking p18(Ink4c) exhibit a series of phenotypes including the development of widespread organomegaly and pituitary adenomas. The objective of our study is to examine the role of p18(INK4C) in the pathogenesis of human pituitary tumors. The protein and mRNA levels of p18(INK4C) were examined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. The methylation status of the p18(INK4C) gene promoter and somatic mutations of the p18(INK4C) gene were also investigated. p18(INK4C) protein expression was lost or significantly reduced in 64% of pituitary adenomas compared with levels in normal pituitary glands. p18(INK4C) mRNA levels were low in all ACTH adenomas and non-functioning (NF)-FSH and in 42%, 70% and 66% of GH, PRL, and subtype 3 adenomas, respectively. p18(INK4C) mRNA levels were significantly associated with p18(INK4C) protein levels. Neither methylated promoters in pituitary adenomas, except in one NF-FSH adenoma, nor somatic mutations of the p18(INK4C) gene in any pituitary adenomas were detected. The down-regulation of p18(INK4C) expression may contribute to the tumorigenesis of pituitary adenomas.
Insights
Loss of p18(INK4C) expression is common in human pituitary tumors, suggesting its role in pituitary adenoma development. Further research is needed to understand this cell cycle regulator
Area of Science:
- Oncology
- Cell Biology
- Endocrinology
Background:
- Cyclin-dependent kinase inhibitors (INK4 family) regulate the cell cycle and are often aberrant in cancer.
- Mice lacking p18(Ink4c) develop pituitary adenomas, indicating its potential role in pituitary tumorigenesis.
Purpose of the Study:
- To investigate the role of p18(INK4C) in the pathogenesis of human pituitary tumors.
- To analyze p18(INK4C) expression, gene promoter methylation, and mutations in pituitary adenomas.
Main Methods:
- Immunohistochemistry to assess p18(INK4C) protein levels.
- Real-time reverse transcription-polymerase chain reaction for p18(INK4C) mRNA quantification.
- Analysis of p18(INK4C) gene promoter methylation and somatic mutations.
Main Results:
- p18(INK4C) protein expression was lost or reduced in 64% of pituitary adenomas compared to normal pituitary glands.
- Low p18(INK4C) mRNA levels were observed in various pituitary adenoma subtypes, correlating with protein levels.
- No significant promoter methylation or somatic mutations of the p18(INK4C) gene were detected in most pituitary adenomas.
Conclusions:
- Down-regulation of p18(INK4C) expression is a frequent event in pituitary adenomas.
- Reduced p18(INK4C) may contribute to the development of pituitary tumors.
- Further studies are warranted to elucidate the precise mechanisms of p18(INK4C) dysregulation in pituitary tumorigenesis.
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