Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors

1993 ◽  
Vol 77 (3) ◽  
pp. 765-769 ◽  
Author(s):  
K. Tordjman
Keyword(s):  
Pituitary Tumors ◽  
Activating Mutations ◽  
Alpha Gene ◽  
Gs Alpha

Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.

1993 ◽  
Vol 77 (3) ◽  
pp. 765-769 ◽  
Author(s):  
K Tordjman ◽  
N Stern ◽  
G Ouaknine ◽  
Y Yossiphov ◽  
N Razon ◽  
...  
Keyword(s):  
Pituitary Tumors ◽  
Activating Mutations ◽  
Alpha Gene ◽  
Gs Alpha

Inactivating and activating mutations of the Gs alpha gene

2005 ◽  
Vol 66 (3) ◽  
pp. 258-263 ◽  
Author(s):  
A. Spada ◽  
G. Mantovani ◽  
A. Lania
Keyword(s):  
Activating Mutations ◽  
Alpha Gene ◽  
Gs Alpha

Activating genomic alterations in the Gs alpha gene ( GNAS ) in 274 694 tumors

2020 ◽  
Vol 59 (9) ◽  
pp. 503-516
Author(s):  
Amit Tirosh ◽  
Dexter X. Jin ◽  
Luiz De Marco ◽  
Yael Laitman ◽  
Eitan Friedman
Keyword(s):  
Genomic Alterations ◽  
Alpha Gene ◽  
Gs Alpha

scholarly journals Activating Mutations of the Gsα Gene Are Associated with Low Levels of Gsα Protein in Growth Hormone-Secreting Tumors1

1998 ◽  
Vol 83 (12) ◽  
pp. 4386-4390 ◽  
Author(s):  
Emilia Ballaré ◽  
Simona Mantovani ◽  
Andrea Lania ◽  
Anna M. Di Blasio ◽  
Lucia Vallar ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Ribonucleic Acid ◽  
Pituitary Tumors ◽  
Acid Synthesis ◽  
Endocrine Tumors ◽  
Wild Type ◽  
Messenger Ribonucleic Acid ◽  
Activating Mutations ◽  
Gsα Gene ◽  
System Data

Evidence suggests the existence of a direct relationship between cellular Gsα content and activation of the adenylyl cyclase system. Data on Gsα levels in endocrine tumors that depend on cAMP for growth, particularly pituitary adenomas, are still limited. The levels of Gsα protein were evaluated in 11 GH-secreting adenomas with Gsα mutations (gsp+) and 15 without (gsp). Complementary DNAs from gsp+ tumors contained very low amounts of wild-type Gsα sequences, indicating a preponderance of the mutant Gsα transcripts in these tumors. Immunoblotting of Gsα protein showed that the two isoforms were present at high levels in all gsp−, but were undetectable or barely detectable in gsp+. The low Gsα content in gsp+ tumors was not due to a reduction in ribonucleic acid synthesis or stability, as Gsα messenger ribonucleic acid levels were similar in wild-type and mutant tissues. Treatment of gsp− cells with cholera toxin caused a marked reduction of Gsα levels. As in other cell systems cholera toxin increases Gsα degradation, our data are consistent with an accelerated removal of mutant Gsα. This may represent an additional mechanism of feedback response to the constitutive activation of cAMP signaling in pituitary tumors with mutations in the Gsα gene.

Cellular alterations in pituitary tumors

1994 ◽  
Vol 130 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Anna Spada ◽  
Lucia Vallar ◽  
Giovanni Faglia
Keyword(s):  
Transcriptional Activation ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Tumor Formation ◽  
Chromosome 1 ◽  
Ras Gene ◽  
Α Subunit ◽  
Activating Mutations ◽  
Almost All ◽  
Cellular Alterations

Spada A, Vallar L, Faglia G. Cellular alterations in pituitary tumors. Eur J Endocrinol 1994;130:43–52. ISSN 0804–4643 In the last few years, molecular studies on pituitary adenomas have yielded evidence supporting a primary pituitary origin of these tumors. Although the existence of genomic alterations in tumoral cells is strongly suggested by the fact that almost all pituitary adenomas are monoclonal in origin, structural genetic abnormalities such as rearrangement, deletion or mutation, which could result in transcriptional activation, have been identified in a minority of tumors. As far as the possible loss of anti-oncogenes in pituitary tumors is concerned, gene alterations have not been found in the p53 nor in the retinoblastoma gene, while loss of chromosome 1 1q13 sequences, which contain the deduced location of the yet uncloned MEN-1 gene, has been reported in a subset of GH-secreting adenomas. With regard to the activation of dominant oncogenes in the process of tumor formation, activating mutations of either the Gs α-subunit or the ras gene have been identified in a large proportion of GH-secreting adenomas and in individual particularly invasive tumours, respectively. Promoting agents such as hypothalamic neurohormones and growth factors may be required for the selective growth of genetically altered cells. In this respect, it is worth noting that receptor/postreceptor alterations occurring in pituitary tumors may cause an increased action of stimulatory neurohormones with growth promoting properties as well as defective action of inhibitory inputs. Anna Spada, Institute of Endocrine Sciences, Pad. Granelli Ospedale Maggiore IRCCS, via F Sforza 35, Milano 20122, Italy

Immunodetection of G proteins in human pituitary adenomas: evidence for a low expression of proteins of the Gi subfamily

1997 ◽  
pp. 482-489 ◽  
Author(s):  
E Ballare ◽  
S Mantovani ◽  
M Bassetti ◽  
A Lania ◽  
A Spada
Keyword(s):  
G Proteins ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Cell Periphery ◽  
Human Pituitary ◽  
Weak Band ◽  
Rat Pituitary ◽  
Normal Human ◽  
Gs Alpha ◽  
Low Expression

G proteins mediate signal transduction in a variety of cell systems. As the expression of these proteins has not yet been investigated in detail in human pituitary tumors, we evaluated the presence of G proteins in a series of tumors including six non-functioning adenomas, five GH-secreting adenomas, three prolactinomas and one TSH-secreting adenoma, using immunoblotting and immunohistochemistry. By immunoblotting, Gi1/2alpha was undetectable in six and barely detectable in nine tumors. A similar pattern of expression was observed by probing with the antibody to Gi3alpha, which detected a very weak band in 11 tumors and no protein in four. In contrast, using large amounts of membrane proteins (40 microg), both Gi1/2alpha and Gi3alpha were detected, although at very low levels, in the negative tumors. The low expression of these proteins appeared to be specific to tumoral tissues, as both Gi1/2alpha and Gi3alpha were abundant in normal human and rat pituitary. In all tumors, Go alpha, the two Gs alpha forms, Gq/11 and G beta were present in significant amounts. Semiquantitative analysis indicated that Gs alpha was clearly detected when 2.5 microg loaded proteins were used, whereas Gi1/2alpha and Gi3alpha were barely detected with 5 microg. By immunofluorescence, all tumors studied were markedly positive for Gs alpha that was immunolocalized at the cell periphery, whereas they showed a weak positivity for Gi1/2alpha and Gi3alpha. The study is the first to provide evidence for a low expression of Gi proteins, which are involved in the transduction of inhibitory signals, in pituitary adenomas.

scholarly journals Parental origin of Gs alpha gene mutations in Albright's hereditary osteodystrophy.

1994 ◽  
Vol 31 (11) ◽  
pp. 835-839 ◽  
Author(s):  
L C Wilson ◽  
M E Oude Luttikhuis ◽  
P T Clayton ◽  
W D Fraser ◽  
R C Trembath
Keyword(s):  
Gene Mutations ◽  
Parental Origin ◽  
Albright’S Hereditary Osteodystrophy ◽  
Albright's Hereditary Osteodystrophy ◽  
Alpha Gene ◽  
Gs Alpha
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