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| Status |
Public on Jul 10, 2013 |
| Title |
Transcriptome analysis of MENX‑associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Gonadotroph adenomas comprise 15–40 % of all pituitary tumors, are usually non-functioning and are often large and invasive at presentation. Surgery is the first-choice treatment, but complete resection is not always achieved, leading to high recurrence rates. As gonadotroph adenomas poorly respond to conventional pharmacological therapies, novel treatment strategies are needed. Their identification has been hampered by our incomplete understanding of the molecular pathogenesis of these tumors. Recently, we dem¬onstrated that MENX-affected rats develop gonadotroph adenomas closely resembling their human counterparts. To discover new genes/pathways involved in gonadotroph cells tumorigenesis, we performed transcriptome profiling of rat tumors versus normal pituitary. Adenomas showed overrep¬resentation of genes involved in cell cycle, development, cell differentiation/proliferation, and lipid metabolism. Bioinfor¬matic analysis identified downstream targets of the transcrip¬tion factor SF-1 as being up-regulated in rat (and human) adenomas. Meta-analyses demonstrated remarkable similari¬ties between gonadotroph adenomas in rats and humans, and highlighted common dysregulated genes, several of which were not previously implicated in pituitary tumorigenesis. Two such genes, CYP11A1 and NUSAP1, were analyzed in 39 human gonadotroph adenomas by qRT-PCR and found to be up-regulated in 77 and 95 % of cases, respectively. Immunohistochemistry detected high P450scc (encoded by CYP11A1) and NuSAP expression in 18 human gonado¬troph tumors. In vitro studies demonstrated for the first time that Cyp11a1 is a target of SF-1 in gonadotroph cells and promotes proliferation/survival of rat pituitary adenoma pri¬mary cells and cell lines. Our studies reveal clues about the molecular mechanisms driving rat and human gonadotroph adenomas development, and may help identify previously unexplored biomarkers for clinical use.
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| Overall design |
We compared five control animals and 16 homozygous mutants (p27Kip1/Cdknb1)
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| Contributor(s) |
Marinoni I, Irmler M, Beckers J, Lee M, Pellegata N |
| Citation(s) |
23756599 |
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| Submission date |
Jul 27, 2010 |
| Last update date |
Dec 18, 2013 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
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| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Experimental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL6247 |
[RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (21)
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| GSM570911 |
Pituitary, biological replicate 4 |
| GSM570912 |
Pituitary, biological replicate 5 |
| GSM570921 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 01 |
| GSM570922 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 02 |
| GSM570923 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 03 |
| GSM570924 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 04 |
| GSM570925 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 05 |
| GSM570926 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 06 |
| GSM570927 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 07 |
| GSM570928 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 08 |
| GSM570929 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 09 |
| GSM570930 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 10 |
| GSM570931 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 11 |
| GSM570932 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 12 |
| GSM570933 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 14 |
| GSM570934 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 15 |
| GSM570935 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 16 |
| GSM570936 |
Pituitary lesion, homozygous for Cdknb1 mutation, biological replicate 17 |
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| Relations |
| BioProject |
PRJNA131639 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23207_RAW.tar |
84.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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