Differential Gene Expressions in Two Histologically Different Types of a Growth Hormone-Releasing Pituitary Adenoma

  • MATSUO Hideo
    Department of Biochemistry Kyorin University School of Medicine
  • YAMADA Shozo
    Department of Neurosurg, Toranomon Hospital
  • NOMURA Akira
    Department of Biochemistry Kyorin University School of Medicine
  • KOH Syunhan
    Department of Biochemistry Kyorin University School of Medicine
  • TAKABATAKE Ichiro
    Department of Biochemistry Kyorin University School of Medicine
  • CHIN Yujin
    Department of Biochemistry Kyorin University School of Medicine
  • TSUCHIYA Katsumi
    Department of Biochemistry Kyorin University School of Medicine
  • SAKAI Tetsuo
    Department of Biochemistry Kyorin University School of Medicine
  • YOSHIE Rika
    Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine
  • MURATA Atsuo
    Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine
  • YOSHIMOTO Katsuhiko
    Department of Molecular Pharmacol, Institute of Health Biosciences, The University of Tokushima Graduate School
  • WAKIZAKA Akira
    Department of Biochemistry Kyorin University School of Medicine

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  • 組織形態学的に異なる二種の下垂体腫瘍における遺伝子発現レベルの差異

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Abstract

Growth hormone (GH)-releasing pituitary tumors are divided into two types, sparsely (S) and densely (D) granulated adenomas, according to their histological features. The former, S-type, is known to be low in releasing GH, but worse in prognosis. For a clearer understanding of the pathophysiological states of these two malignancies, we analyzed the difference in their-gene expression levels using a Clontech model Atlas Human 1.2 Array. RNA was prepared from post-operative tissue specimen obtained from patients under informed consent. Fifty genes (4.25%) out of 1176 genes on the array showed a difference in the expression levels between the two GH cell adenomas. The S-type tumor showed higher expression in several genes involved in cell adhesion, cellular signal transduction, and DNA replication, repair, and recombination processes, compared with the D-type tumor. Among cell adhesion molecules in the S-type tumor, cadherin genes were up-regulated while catenin genes, in paticular, the junction plakoglobin gene (JUP), were down-regulated. The ratio of Bax/Bcl-2. which indicates an apoptosis inducing ability of the cell, was lower in the S-type adenomas. Growth factor and its receptor genes scarcely exhibited the differential expression. However, in the S-type adenoma, some genes related to adaptors, transcription factors, cell-cycle promotion, and oncogenes were up-regulated, while other genes were down-regulated. These results show the structural specificity and malignant nature of the sparsely granulated type of growth hormone-releasing pituitary adenomas.

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