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Absence of activating mutations of <i>CXCR4</i> in pituitary tumours
Lee, Yong-ho,Noh, Tae Woong,Lee, Mi Kyung,Jameson, J. Larry,Lee, Eun Jig Blackwell Publishing Ltd 2010 Clinical endocrinology Vol.72 No.2
<P>Summary</P><P>Objective </P><P>Mutations of the <I>gsp</I> 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.</P><P>Patients and methods </P><P>We investigated whether somatic activating-mutations of <I>CXCR4</I> might be a possible tumourigenic mechanism for <I>gsp</I>-negative GH-secreting pituitary adenomas and NFPAs. Direct sequencing of polymerase chain reaction-amplified products for coding exons of <I>CXCR4</I> were performed using genomic deoxyribonucleic acid samples from 37 GH-producing pituitary tumour tissues that were negative for the <I>gsp</I> mutation and 14 CXCR4 expressing NFPAs.</P><P>Results </P><P>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.</P><P>Conclusion </P><P>Our results indicate that an activating mutation of the <I>CXCR4</I> may not be a common pathogenetic mechanism in GH-producing pituitary tumours and NFPAs.</P>