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PMID: 20811506 Published · ppublish English Journal Article

A Postnatal Pax7 Progenitor Gives Rise to Pituitary Adenomas.

Genes & cancer ·Vol. 1 ·No. 4 ·2010-04-01 ·Pages 388-402

Hosoyama T, Nishijo K, Garcia MM, Schaffer BS, Ohshima-Hosoyama S, Prajapati SI, Davis MD, Grant WF, Scheithauer BW, Marks DL, Rubin BP, Keller C

Abstract

Pituitary adenomas are classified into functioning and nonfunctioning (silent) tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis and the cell of origin for pituitary adenoma subtypes remain to be elucidated. Employing a tamoxifen-inducible mouse model, we demonstrate that a novel postnatal Pax7(+) progenitor cell population in the pituitary gland gives rise to silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is conditionally deleted. While Pax transcriptional factors are critical for embryonic patterning as well as postnatal stem cell renewal for many organs, we have discovered that Pax7 marks a restricted cell population in the postnatal pituitary intermediate lobe. This Pax7(+) early progenitor cell population is overlapping but ontologically downstream of the Nestin(+) pituitary stem cell population, yet upstream of another newly discovered Myf6(+) late progenitor cell population. Interestingly, the Pax7(+) progenitor cell population is evolutionarily conserved in primates and humans, and Pax7 expression is maintained not only in murine tumors but also in human functioning and silent corticotropinomas. Taken together, our results strongly suggest that human silent corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate lobe, a region of the human pituitary bearing closer scientific interest as a reservoir of pituitary progenitor cells.

Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hosoyama Tohru
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA.
Nishijo Koichi
Garcia Melinda M
Schaffer Beverly S
Ohshima-Hosoyama Sachiko
Prajapati Suresh I
Davis Michael D
Grant Wilmon F
Scheithauer Bernd W
Marks Daniel L
Rubin Brian P
Keller Charles
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Article Info
Journal
Genes & cancer
Abbr.
Genes Cancer
ISSN
1947-6019
DOI
10.1177/1947601910370979
Published
2010-04-01
Pages
388-402
Language
English
Region
United States
NLM ID
101516546
PMCID
PMC2930793
Grants
NCRR NIH HHS · P41 RR012553 · United States
NCI NIH HHS · R01 CA133229 · United States
NCI NIH HHS · R01 CA133229-03 · United States
External Links
PubMed source DOI: 10.1177/1947601910370979 PMC Full Text
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