Conditional Pten knock-out mice: a model for metastatic phaeochromocytoma.
Phaeochromocytomas (PCCs) are neuro-endocrine tumours of the adrenal medulla that are usually benign, but approximately 10% of patients develop metastases. Malignant PCCs can only be diagnosed with certainty if metastases are present. Here we describe adrenal tumours generated in a Pten conditional knock-out (KO) mouse model. We characterized the molecular alterations in these tumours and compared them with human PCC. Thirty-two of 41 (78%) male Psa-Cre;Pten-loxP/loxP mice presented adrenal tumours that were shown to be PCC by histology and by immunohistochemical staining for enzymes in the catecholamine biosynthetic pathway. In 6 of 17 investigated mice, histological and immunohistochemical evidence was obtained for the presence of PCC lung metastases. Array comparative genomic hybridization (CGH) analysis of the primary tumours showed loss of chromosomes 6 and 19, which are syntenic to human 3p and 11q. Another frequent alteration found was gain of chromosome 15, which is syntenic to human chromosome 5. The molecular aberrations in the mouse model corresponded to the alterations found in a subtype of human PCC, suggesting that the PCC of the Pten KO mice might be representative of human PCC. The mouse model should allow further studies into the pathogenesis of human malignant PCCs and into therapeutic strategies for these tumours.
Korpershoek
Esther
E
Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Loonen
Anne J M
AJ
Corvers
Suzanne
S
van Nederveen
Francien H
FH
Jonkers
Jos
J
Ma
Xiaoqian
X
Ziel-van der Made
Angelique
A
Korsten
Hanneke
H
Trapman
Jan
J
Dinjens
Winand N M
WN
de Krijger
Ronald R
RR
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D055028:Comparative Genomic Hybridization; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D018807:Polymorphism, Single-Stranded Conformational
D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human