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Isolation and characterization of novel pituitary tumor related genes: a cDNA representational difference approach
Xun Zhang1, Yunli Zhou, Anne Klibanski
1Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
Recently, progress has been made in understanding human pituitary tumor pathogenesis by the investigation of differences in gene expression between normal pituitary tissue and pituitary tumors. A number of approaches, including differential display (DD), representational difference analysis (RDA), and microarray analysis have been used and several molecular targets potentially associated with pituitary tumor development and invasion have been identified. We have used RDA to compare gene expression patterns between normal human pituitary and clinically non-functioning pituitary adenomas, and identified genes with growth suppression function which are expressed in the normal pituitary but not in pituitary tumors. In particular, we have focused on an imprinted gene, Maternally Expressed Gene 3 (MEG3), which is specifically associated with clinically non-functioning pituitary adenomas of a gonadotroph lineage. MEG3 functions to suppress tumor cell growth, increase protein expression of the tumor suppressor p53, and selectively activate p53 target genes. Interestingly, MEG3 does not encode a protein but a non-coding RNA. Therefore, these studies have revealed novel mechanisms for the function of a non-coding RNA in pituitary physiology and tumorigenesis.
Insights
Researchers identified Maternally Expressed Gene 3 (MEG3), a non-coding RNA, as crucial in suppressing pituitary tumor growth. Loss of MEG3 expression is linked to non-functioning pituitary adenomas, revealing new insights into tumor pathogenesis.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Pituitary tumor pathogenesis is increasingly understood through gene expression differences between normal and tumor tissues.
- Techniques like representational difference analysis (RDA) have identified molecular targets in pituitary tumor development.
Purpose of the Study:
- To investigate gene expression patterns in normal pituitary tissue versus non-functioning pituitary adenomas.
- To identify genes with growth suppression functions absent in pituitary tumors.
Main Methods:
- Representational difference analysis (RDA) was employed to compare gene expression profiles.
- Focus was placed on imprinted genes, specifically Maternally Expressed Gene 3 (MEG3).
Main Results:
- Genes with growth suppression functions were identified in normal pituitary tissue but not in tumors.
- Maternally Expressed Gene 3 (MEG3), a non-coding RNA, was specifically associated with non-functioning pituitary adenomas of gonadotroph lineage.
- MEG3 demonstrated tumor suppressor activity by inhibiting cell growth and upregulating p53 expression and activity.
Conclusions:
- Maternally Expressed Gene 3 (MEG3) functions as a non-coding RNA with a critical role in suppressing pituitary tumor growth.
- The loss of MEG3 expression is implicated in the development of non-functioning pituitary adenomas.
- These findings highlight novel mechanisms of non-coding RNA function in pituitary physiology and tumorigenesis.
