Parathyroid tumor development involves deregulation of homeobox genes

H. C Jennifer Shen, Jennifer E. Rosen, Lauren M. Yang, Sharon A. Savage, A. Lee Burns, Carmen M. Mateo, Sunita K. Agarwal, Settara C. Chandrasekharappa, Allen M. Spiegel, Francis S. Collins, Stephen J. Marx, Steven K. Libutti

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome caused by mutations in the MEN1 tumor suppressor gene. Loss of the functional second copy of the MEN1 gene causes individuals to develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and pancreas. While it is clear that the protein encoded by MEN1, menin, suppresses endocrine tumors, its biochemical functions and direct downstream targets remain unclear. Recent studies have suggested that menin may act as a scaffold protein to coordinate gene transcription, and that menin is an oncogenic cofactor for homeobox (HOX) gene expression in hematopoietic cancer. The role of HOX genes in adult cell differentiation is still obscure, but growing evidence suggests that they may play important roles in the development of cancer. Therefore, we hypothesized that specific HOX genes were regulated by menin in parathyroid tumor development. Utilizing quantitative TaqMan RT-PCR, we compared expression profiles of the 39 HOX genes in human familial MEN1 (fMEN1) parathyroid tumors and sporadic parathyroid adenomas with normal samples. We identified a large set of 23 HOX genes whose deregulation is specific for fMEN1 parathyroid tumors, and only 5 HOX genes whose misexpression are specific for sporadic parathyroid tumor development. These findings provide the first evidence that loss of the MEN1 tumor suppressor gene is associated with deregulation of specific HOX gene expression in the development of familial human parathyroid tumors. Our results strongly reinforce the idea that abnormal expression of developmental HOX genes can be critical in human cancer progression.

Original languageEnglish (US)
Pages (from-to)267-275
Number of pages9
JournalEndocrine-Related Cancer
Volume15
Issue number1
DOIs
StatePublished - Mar 2008

Fingerprint

Homeobox Genes
Multiple Endocrine Neoplasia Type 1
Neoplasms
Tumor Suppressor Genes
Developmental Genes
Gene Expression
Parathyroid Neoplasms
Human Development
Genes
Cell Differentiation
Pancreas
Proteins
Polymerase Chain Reaction
Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Shen, H. C. J., Rosen, J. E., Yang, L. M., Savage, S. A., Burns, A. L., Mateo, C. M., ... Libutti, S. K. (2008). Parathyroid tumor development involves deregulation of homeobox genes. Endocrine-Related Cancer, 15(1), 267-275. https://doi.org/10.1677/ERC-07-0191

Parathyroid tumor development involves deregulation of homeobox genes. / Shen, H. C Jennifer; Rosen, Jennifer E.; Yang, Lauren M.; Savage, Sharon A.; Burns, A. Lee; Mateo, Carmen M.; Agarwal, Sunita K.; Chandrasekharappa, Settara C.; Spiegel, Allen M.; Collins, Francis S.; Marx, Stephen J.; Libutti, Steven K.

In: Endocrine-Related Cancer, Vol. 15, No. 1, 03.2008, p. 267-275.

Research output: Contribution to journalArticle

Shen, HCJ, Rosen, JE, Yang, LM, Savage, SA, Burns, AL, Mateo, CM, Agarwal, SK, Chandrasekharappa, SC, Spiegel, AM, Collins, FS, Marx, SJ & Libutti, SK 2008, 'Parathyroid tumor development involves deregulation of homeobox genes', Endocrine-Related Cancer, vol. 15, no. 1, pp. 267-275. https://doi.org/10.1677/ERC-07-0191
Shen HCJ, Rosen JE, Yang LM, Savage SA, Burns AL, Mateo CM et al. Parathyroid tumor development involves deregulation of homeobox genes. Endocrine-Related Cancer. 2008 Mar;15(1):267-275. https://doi.org/10.1677/ERC-07-0191
Shen, H. C Jennifer ; Rosen, Jennifer E. ; Yang, Lauren M. ; Savage, Sharon A. ; Burns, A. Lee ; Mateo, Carmen M. ; Agarwal, Sunita K. ; Chandrasekharappa, Settara C. ; Spiegel, Allen M. ; Collins, Francis S. ; Marx, Stephen J. ; Libutti, Steven K. / Parathyroid tumor development involves deregulation of homeobox genes. In: Endocrine-Related Cancer. 2008 ; Vol. 15, No. 1. pp. 267-275.
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