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Absence of activating mutations of CXCR4 in pituitary tumours.

 Yong-ho Lee  ;  Tae Woong Noh  ;  Mi Kyung Lee  ;  J. Larry Jameson  ;  Eun Jig Lee 
 CLINICAL ENDOCRINOLOGY, Vol.72(2) : 209-213, 2010 
Journal Title
Issue Date
Growth Hormone-Secreting Pituitary Adenoma/genetics ; Growth Hormone-Secreting Pituitary Adenoma/metabolism ; Humans ; Immunohistochemistry ; Mutation ; Pituitary Neoplasms/genetics* ; Pituitary Neoplasms/metabolism* ; Polymerase Chain Reaction ; Receptors, CXCR4/genetics* ; Receptors, CXCR4/metabolism*
OBJECTIVE: Mutations of the gsp oncogene are responsible for 30-40% of GH-producing pituitary adenomas and 10% of nonfunctioning pituitary adenomas (NFPAs). However, the pathogenetic mechanism of the remaining pituitary tumours still remains to be identified. Recently, the interaction between the chemokine stromal cell-derived factor 1 and its receptor CXCR4 was found to play an important role in GH production and cell proliferation in various pituitary adenoma cell lines. As CXCR4 is a Gi-coupled chemokine receptor, its constitutive activating mutations may be involved in pituitary tumour formation by cyclic adenosine monophosphate (cAMP)-independent, ERK-related pathways. PATIENTS AND METHODS: We investigated whether somatic activating-mutations of CXCR4 might be a possible tumourigenic mechanism for gsp-negative GH-secreting pituitary adenomas and NFPAs. Direct sequencing of polymerase chain reaction-amplified products for coding exons of CXCR4 were performed using genomic deoxyribonucleic acid samples from 37 GH-producing pituitary tumour tissues that were negative for the gsp mutation and 14 CXCR4 expressing NFPAs. RESULTS: Immunohistochemical analyses and double immunofluorescent staining of sectioned paraffin-embedded pituitary tissues revealed that CXCR4 is highly expressed in GH-producing pituitary adenomas and NFPAs. Direct sequencing showed that two synonymous mutations in exon 2 (87 C > T and 414 C > T) were detected in 4 out of 51 pituitary tumours. CONCLUSION: Our results indicate that an activating mutation of the CXCR4 may not be a common pathogenetic mechanism in GH-producing pituitary tumours and NFPAs.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Tae Woong(노태웅)
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
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