Abstract
In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsα gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsα, have been proposed to account for the lack of genotype/phenotype relationships.
| Original language | English |
|---|---|
| Pages (from-to) | 1004-1017 |
| Number of pages | 14 |
| Journal | Experimental Biology and Medicine |
| Volume | 228 |
| Issue number | 9 |
| Publication status | Published - Oct 2003 |
Fingerprint
Keywords
- cAMP
- gsp
- Oncogene
- Pituitary adenomas
- Tumor suppressor genes genes
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Genetics of pituitary tumors : Focus on G-protein mutations. / Lania, Andrea; Mantovani, Giovanna; Spada, Anna.
In: Experimental Biology and Medicine, Vol. 228, No. 9, 10.2003, p. 1004-1017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetics of pituitary tumors
T2 - Focus on G-protein mutations
AU - Lania, Andrea
AU - Mantovani, Giovanna
AU - Spada, Anna
PY - 2003/10
Y1 - 2003/10
N2 - In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsα gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsα, have been proposed to account for the lack of genotype/phenotype relationships.
AB - In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsα gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsα, have been proposed to account for the lack of genotype/phenotype relationships.
KW - cAMP
KW - gsp
KW - Oncogene
KW - Pituitary adenomas
KW - Tumor suppressor genes genes
UR - http://www.scopus.com/inward/record.url?scp=0141864375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141864375&partnerID=8YFLogxK
M3 - Article
VL - 228
SP - 1004
EP - 1017
JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
SN - 0037-9727
IS - 9
ER -