PMID- 18310293
OWN - NLM
STAT- MEDLINE
DCOM- 20080508
LR  - 20211020
IS  - 1351-0088 (Print)
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 15
IP  - 1
DP  - 2008 Mar
TI  - Parathyroid tumor development involves deregulation of homeobox genes.
PG  - 267-75
LID - 10.1677/ERC-07-0191 [doi]
AB  - 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.
FAU - Shen, H-C Jennifer
AU  - Shen HC
AD  - Tumor Angiogenesis Section, Surgery Branch, National Cancer Institute, NIH, 
      Bethesda, MD 20892, USA.
FAU - Rosen, Jennifer E
AU  - Rosen JE
FAU - Yang, Lauren M
AU  - Yang LM
FAU - Savage, Sharon A
AU  - Savage SA
FAU - Burns, A Lee
AU  - Burns AL
FAU - Mateo, Carmen M
AU  - Mateo CM
FAU - Agarwal, Sunita K
AU  - Agarwal SK
FAU - Chandrasekharappa, Settara C
AU  - Chandrasekharappa SC
FAU - Spiegel, Allen M
AU  - Spiegel AM
FAU - Collins, Francis S
AU  - Collins FS
FAU - Marx, Stephen J
AU  - Marx SJ
FAU - Libutti, Steven K
AU  - Libutti SK
LA  - eng
GR  - ZIA CP010142-11/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Homeobox/*genetics
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/metabolism/pathology
MH  - Mutation/*genetics
MH  - Parathyroid Neoplasms/genetics/*metabolism/*pathology
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC3133970
MID - NIHMS301793
EDAT- 2008/03/04 09:00
MHDA- 2008/05/09 09:00
PMCR- 2011/07/12
CRDT- 2008/03/04 09:00
PHST- 2008/03/04 09:00 [pubmed]
PHST- 2008/05/09 09:00 [medline]
PHST- 2008/03/04 09:00 [entrez]
PHST- 2011/07/12 00:00 [pmc-release]
AID - 15/1/267 [pii]
AID - 10.1677/ERC-07-0191 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2008 Mar;15(1):267-75. doi: 10.1677/ERC-07-0191.