A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.
Human pituitary adenomas are the most common intracranial neoplasm. Typically monoclonal in origin, a somatic mutation is a prerequisite event in tumor development. To identify underlying pathogenetic mechanisms in tumor formation, we compared the difference in gene expression between normal human pituitary tissue and clinically nonfunctioning pituitary adenomas by cDNA-representational difference analysis. We cloned a cDNA, the expression of which was absent in these tumors, that represents a novel transcript from the previously described MEG3, a maternal imprinting gene with unknown function. It was expressed in normal human gonadotrophs, from which clinically nonfunctioning pituitary adenomas are derived. Additional investigation by Northern blot and RT-PCR demonstrated that this gene was also not expressed in functioning pituitary tumors as well as many human cancer cell lines. Moreover, ectopic expression of this gene inhibits growth in human cancer cells including HeLa, MCF-7, and H4. Genomic analysis revealed that MEG3 is located on chromosome 14q32.3, a site that has been predicted to contain a tumor suppressor gene involved in the pathogenesis of meningiomas. Taken together, our data suggest that MEG3 may represent a novel growth suppressor, which may play an important role in the development of human pituitary adenomas.
Zhang
Xun
X
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114,USA
Zhou
Yunli
Y
Mehta
Kshama R
KR
Danila
Daniel C
DC
Scolavino
Staci
S
Johnson
Stacey R
SR
Klibanski
Anne
A
D000236:Adenoma / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D001943:Breast Neoplasms; D002455:Cell Division; D003001:Cloning, Molecular; D018076:DNA, Complementary; D016147:Genes, Tumor Suppressor; D005910:Glioma; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000503:physiopathology; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding
D018076:DNA, Complementary; C498907:MEG3 non-coding RNA, human; D011506:Proteins; D062085:RNA, Long Noncoding