Absence of activating mutations of CXCR4 in pituitary tumours

Yong Ho Lee, Tae Woong Noh, Mi Kyung Lee, J. Larry Jameson, Eunjig Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)209-213
Number of pages5
JournalClinical Endocrinology
Volume72
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

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Pituitary Neoplasms
Mutation
Exons
Growth Hormone-Secreting Pituitary Adenoma
CXCR4 Receptors
Chemokine CXCL12
MAP Kinase Signaling System
Chemokine Receptors
Oncogenes
Chemokines
Cyclic AMP
Paraffin
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Lee, Yong Ho ; Noh, Tae Woong ; Lee, Mi Kyung ; Jameson, J. Larry ; Lee, Eunjig. / Absence of activating mutations of CXCR4 in pituitary tumours. In: Clinical Endocrinology. 2010 ; Vol. 72, No. 2. pp. 209-213.
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Absence of activating mutations of CXCR4 in pituitary tumours. / Lee, Yong Ho; Noh, Tae Woong; Lee, Mi Kyung; Jameson, J. Larry; Lee, Eunjig.

In: Clinical Endocrinology, Vol. 72, No. 2, 01.02.2010, p. 209-213.

Research output: Contribution to journalArticle

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T1 - Absence of activating mutations of CXCR4 in pituitary tumours

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AU - Noh, Tae Woong

AU - Lee, Mi Kyung

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N2 - 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.

AB - 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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