A postnatal pax7+ progenitor gives rise to pituitary adenomas

Tohru Hosoyama, Koichi Nishijo, Melinda M. Garcia, Beverly S. Schaffer, Sachiko Ohshima-Hosoyama, Suresh I. Prajapati, Michael D. Davis, Wilmon F. Grant, Bernd W. Scheithauer, Daniel L. Marks, Brian P. Rubin, Charles Keller

Research output: Contribution to journalArticle

41 Scopus citations

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 zntermediate lobe, a region of the human pituitarybearing closer scientific interest as a reservoir of pituitary progenitor cells.

Original languageEnglish (US)
Pages (from-to)388-402
Number of pages15
JournalGenes and Cancer
Volume1
Issue number4
DOIs
StatePublished - 2010

Keywords

  • Corticotroph
  • Melanotroph
  • Myf6
  • Pax7
  • Pituitary macro-adenoma
  • pRb

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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    Hosoyama, T., Nishijo, K., Garcia, M. M., Schaffer, B. S., Ohshima-Hosoyama, S., Prajapati, S. I., Davis, M. D., Grant, W. F., Scheithauer, B. W., Marks, D. L., Rubin, B. P., & Keller, C. (2010). A postnatal pax7+ progenitor gives rise to pituitary adenomas. Genes and Cancer, 1(4), 388-402. https://doi.org/10.1177/1947601910370979