ORIGINAL ARTICLE

Age related expression of Werner's syndrome protein in selected tissues and coexpression of transcription factors

K Motonaga¹, M Itoh¹, Y Hachiya³, A Endo³, K Kato⁴, H Ishikura⁴, Y Saito⁵, S Mori⁵, S Takashima² and Y Goto¹

¹ Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, 4–1–1 Ogawahigashi, Kodaira, Tokyo 187–8502, Japan
² National Institute of Neuroscience, National Center of Neurology and Psychiatry
³ Department of Clinical Laboratory, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry
⁴ Department of Pathology, Chiba University School of Medicine, 1-8-1 Inohana, Chiba 260–0856, Japan
⁵ The Second Department of Internal Medicine, Chiba University School of Medicine

Correspondence to:
Correspondence to:
Dr K Motonaga, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4–1–1 Ogawahigashi, Kodaira, Tokyo 187–8502, Japan;
motonaga{at}ncnp.go.jp

Aims: Werner's syndrome (WS) is an uncommon autosomal recessive disease resulting from mutational inactivation of human WRN helicase, Werner's syndrome protein (WRNp). Patients with WS progressively develop a variety of aging characteristics after puberty. The aim of this study was to determine the distribution of WRNp and the expression of the transcription factors regulating WRN gene expression in a variety of human organs in an attempt to understand the WS phenotype.

Methods: Tissue specimens were obtained from 16 controls aged from 27 gestational weeks to 70 years of age and a 56 year old female patient with WS. The distribution of WRNp and the expression of the transcription factors regulating WRN gene expression—SP1, AP2, and retinoblastoma protein (Rb)— were studied in the various human organs by immunohistochemical and immunoblot analyses.

Results: In the healthy controls after puberty, high expression of WRNp was detected in seminiferous epithelial cells and Leydig cells in the testis, glandular acini in the pancreas, and the zona fasciculata and zona reticularis in the adrenal cortex. In addition, the SP1 and AP2 transcription factors, which regulate WRNp gene expression, appeared in an age dependent manner in those regions where WRNp was expressed. In controls after puberty, SP1 was expressed in the testis and adrenal gland, whereas AP2 was expressed in the pancreas.

Conclusions: These findings suggest that the age specific onset of WS may be related to age dependent expression of WRNp in specific organs.

Keywords: Werner's syndrome; Werner's syndrome protein; SP1; AP2

Abbreviations: BLM, Bloom syndrome; DHEA-S, dehydroepiandrosterone sulphate; Rb, retinoblastoma protein; RCE, retinoblastoma control element; RTS, Rothmund-Thomson syndrome; WS, Werner's syndrome; WRNp, Werner's syndrome protein

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