Parathyroid tumor development involves deregulation of homeobox genes
H-C Jennifer Shen1, Jennifer E Rosen, Lauren M Yang
1Tumor Angiogenesis Section, Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Endocrine-Related Cancer
|March 4, 2008
Summary
Multiple endocrine neoplasia type 1 (MEN1) involves mutations in the MEN1 gene. This study reveals that MEN1 gene loss deregulates specific HOX genes in parathyroid tumors, impacting cancer progression.
Area of Science:
- Endocrinology
- Cancer Biology
- Genetics
Background:
- Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome linked to MEN1 gene mutations.
- The menin protein, encoded by MEN1, is known to suppress endocrine tumors, but its precise functions and targets are not fully understood.
- HOX genes are implicated in cancer development, but their role in endocrine tumorigenesis is unclear.
Purpose of the Study:
- To investigate the hypothesis that menin regulates specific HOX genes in parathyroid tumor development.
- To identify HOX gene expression profiles associated with familial MEN1 (fMEN1) parathyroid tumors.
Main Methods:
- Quantitative TaqMan RT-PCR was used to analyze the expression of all 39 HOX genes.
- Expression profiles were compared between human fMEN1 parathyroid tumors, sporadic parathyroid adenomas, and normal parathyroid samples.
Main Results:
- A distinct set of 23 HOX genes showed deregulation specific to fMEN1 parathyroid tumors.
- Only 5 HOX genes exhibited misexpression specific to sporadic parathyroid tumor development.
- This is the first evidence linking MEN1 tumor suppressor gene loss to HOX gene deregulation in familial human parathyroid tumors.
Conclusions:
- Loss of the MEN1 tumor suppressor gene is associated with altered expression of specific HOX genes in familial parathyroid tumor development.
- Abnormal HOX gene expression may be critical in the progression of human endocrine cancers.
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