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Expression of p18INK4C is Down-regulated in Human Pituitary Adenomas

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Abstract

Cyclin-dependent kinase inhibitors represented by the INK4 family comprising p16INK4A, p15INK4B, p18INK4C, and p19INK4D are regulators of the cell cycle shown to be aberrant in many types of cancer. Mice lacking p18Ink4c 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 p18INK4C in the pathogenesis of human pituitary tumors. The protein and mRNA levels of p18INK4C were examined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. The methylation status of the p18INK4C gene promoter and somatic mutations of the p18INK4C gene were also investigated. p18INK4C protein expression was lost or significantly reduced in 64% of pituitary adenomas compared with levels in normal pituitary glands. p18INK4C 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. p18INK4C mRNA levels were significantly associated with p18INK4C protein levels. Neither methylated promoters in pituitary adenomas, except in one NF-FSH adenoma, nor somatic mutations of the p18INK4C gene in any pituitary adenomas were detected. The down-regulation of p18INK4C expression may contribute to the tumorigenesis of pituitary adenomas.

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Acknowledgment

This work was supported in part by a grant from the Foundation for Growth Science.

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Authors and Affiliations

  1. Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    Md. Golam Hossain, Takeo Iwata, Noriko Mizusawa, Shahidan Wan Nazatul Shima & Katsuhiko Yoshimoto

  2. Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    Zhi Rong Qian & Toshiaki Sano

  3. Department of Oral and Maxillofacial Prosthodontics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    Toru Okutsu

  4. Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan

    Shozo Yamada

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  1. Md. Golam Hossain
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  2. Takeo Iwata
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Correspondence to Katsuhiko Yoshimoto.

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Hossain, M.G., Iwata, T., Mizusawa, N. et al. Expression of p18INK4C is Down-regulated in Human Pituitary Adenomas. Endocr Pathol 20, 114–121 (2009). https://doi.org/10.1007/s12022-009-9076-0

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