Molecular pathogenesis of human prolactinomas identified by gene expression profiling, RT-qPCR, and proteomic analyses.

Abstract:

:The molecular pathogenesis of prolactinomas has resisted elucidation; with the exception of a RAS mutation in a single aggressive prolactinoma, no mutational changes have been identified. In prolactinomas, a further obstacle has been the paucity of surgical specimens suitable for molecular analysis since prolactionomas are infrequently removed due to the availability and effectiveness of medical therapy. In the absence of mutational events, gene expression changes have been sought and detected. Using high-throughput analysis from a large bank of human pituitary adenomas, we examined these tumors according to their molecular profiles rather than traditional immunohistochemistry. We examined six prolactinomas and eight normal pituitary glands using oligonucleotide GeneChip microarrays, reverse transcription-real time quantitative polymerase chain reaction using 10 prolactinomas, and proteomic analysis to examine protein expression in four prolactinomas. Microarray analyses identified 726 unique genes that were statistically significantly different between prolactinomas and normal glands, whereas proteomic analysis identified four differently up-regulated and 19 down-regulated proteins. Several components of the Notch pathway were altered in prolactinomas, and there was an increased expression of the Pit-1 transcription factor, and the survival factor BAG1 but decreased E-cadherin and N-cadherin expression. Taken together, expression profiling and proteomic analyses have identified molecular features unique to prolactinomas that may contribute to their pathogenesis. In the current era of molecular medicine, these findings greatly enhance our understanding and supercede immunohistochemical diagnosis.

journal_name

Pituitary

journal_title

Pituitary

authors

Evans CO,Moreno CS,Zhan X,McCabe MT,Vertino PM,Desiderio DM,Oyesiku NM

doi

10.1007/s11102-007-0082-2

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

231-45

issue

3

eissn

1386-341X

issn

1573-7403

journal_volume

11

pub_type

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