Inactivation of the p16 Gene in Human Pituitary Nonfunctioning Tumors by Hypermethylation Is More Common in Null Cell Adenomas

2001 ◽  
Vol 12 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Katharina H Ruebel ◽  
Long Jin ◽  
Shuya Zhang ◽  
Bernd W Scheithauer ◽  
Ricardo V Lloyd
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
P16 Gene ◽  
Null Cell Adenomas

Null cell adenomas, oncocytomas, and gonadotroph adenomas of the human pituitary: An immunocytochemical and ultrastructural anafysis of 300 cases

1993 ◽  
Vol 4 (1) ◽  
pp. 20-27 ◽  
Author(s):  
George Kontogeorgos ◽  
Kalman Kovacs ◽  
Eva Horvath ◽  
Bernd W. Scheithauer
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
Null Cell Adenomas

Gonadotropin Secretion in Vitro by Human Pituitary Null Cell Adenomas and Oncocytomas**

1986 ◽  
Vol 62 (5) ◽  
pp. 1011-1019 ◽  
Author(s):  
SYLVIA L. ASA ◽  
BLAIR M. GERRIE ◽  
WILLIAM SINGER ◽  
EVA HORVATH ◽  
KALMAN KOVACS ◽  
...  
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
Gonadotropin Secretion ◽  
Null Cell Adenomas

scholarly journals Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas

1999 ◽  
pp. 250-255 ◽  
Author(s):  
CM Bamberger ◽  
M Fehn ◽  
AM Bamberger ◽  
DK Ludecke ◽  
FU Beil ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Cellular Proliferation ◽  
Cell Types ◽  
Null Cell ◽  
Human Pituitary ◽  
Expression Levels ◽  
Cell Cycle Inhibitor ◽  
Null Cell Adenomas

The molecular mechanisms leading to increased cellular proliferation rates and, thus, tumor formation in the anterior pituitary gland are poorly understood. The cyclin-dependent kinase inhibitor p27Kip1 is a key molecule regulating the G1 phase of the cell cycle in many cell types. Furthermore, it was shown that p27 knock-out mice develop pro-opiomelanocortin-positive pituitary tumors. In an effort to clarify the role of p27 in the normal and tumorous human pituitary, we studied the expression of p27 by immunohistochemistry, using a highly specific mouse monoclonal anti-human p27 antibody. Normal pituitaries and 54 pituitary adenomas (twelve somatotrope adenomas, nine prolactinomas, twelve corticotrope adenomas, three TSH-producing tumors, six gonadotrope adenomas, six null cell adenomas, and six oncocytomas) were analyzed. p27 expression was determined semiquantitatively with regard to both the percentage of positive cells and the intensity of the staining. Normal human pituitaries showed strong expression of p27 in most nuclei. In contrast, the levels of p27 were reduced in the majority of the tumors analyzed. Twenty-two tumors (six somatotrope adenomas, five prolactinomas, four corticotrope adenomas, two TSH-producing tumors, two gonadotrope adenomas, and three null cell adenomas) were completely p27-negative. In 18 tumors, p27 expression was found in < or = 10% of the cells. In the other ten tumors, 11-80% of the cells were p27-positive. In summary, we were able to demonstrate reduced expression levels of the cell-cycle inhibitor p27 in tumors derived from all pituitary cell types. Our data indicate that p27 may be an important regulator of cellular proliferation in the anterior pituitary, the underexpression of which could play a role in pituitary tumorigenesis.

scholarly journals Clinically Non-Functioning Human Pituitary Adenomas

1992 ◽  
Vol 19 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Sylvia L. Asa ◽  
Kalman Kovacs
Keyword(s):  
Pituitary Adenomas ◽  
Cell Types ◽  
Null Cell ◽  
Human Pituitary ◽  
Endocrine Activity ◽  
Hormone Synthesis ◽  
A Subunit ◽  
Null Cell Adenomas

ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the fomer are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non-functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell adenomas. We suggest that null cell adenomas and oncocytomas originate in uncommitted pluripotent precursor cells capable of undergoing multidirectional differentiation. The progenitor cells differentiate most frequently toward FSH / a-subunit producing cells; the mechanism of preferential differentiation is obscure.

scholarly journals Reprimo (RPRM) Is a Novel Tumor Suppressor in Pituitary Tumors and Regulates Survival, Proliferation, and Tumorigenicity

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 2963-2973 ◽  
Author(s):  
Mei Xu ◽  
Aaron J. Knox ◽  
Katherine A. Michaelis ◽  
Katja Kiseljak-Vassiliades ◽  
Bette K. Kleinschmidt-DeMasters ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Suppressor ◽  
Cellular Stress ◽  
Pituitary Tumors ◽  
Tumor Formation ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Null Cell ◽  
Human Pituitary ◽  
Protein Levels

Reprimo (RPRM), initially identified as a downstream effector of p53-induced cell cycle arrest at G2/M, is a putative tumor suppressor silenced in some types of cancer. In microarrays, the RPRM transcript was repressed 26-fold in gonadotrope (null cell) human pituitary tumors compared with normal pituitary but in the absence of changes in p53. Inhibition of RPRM mRNA was confirmed by RT-PCR in all gonadotrope tumors, most GH samples, and variably in other tumor types. Human pituitary tumors showed no evidence of abnormal promoter hypermethylation as a mechanism of RPRM repression. RPRM stable expression in gonadotrope (LβT2) and GH (GH3) pituitary cells resulted in decreased rates of cell proliferation by 55 and 30%, respectively; however, RPRM reexpression did not alter G2/M transition. In addition, RPRM increased rates of apoptosis in response to growth factor deprivation as assessed by caspase-3 cleavage and nuclear condensation. Clonagenic assays showed a 5.3- and 3.7-fold suppression of colony growth in RPRM-overexpressing LβT2 and GH3 cells, respectively, supporting its role as a tumor suppressor. In cells stably expressing RPRM mRNA, protein levels were actively suppressed due to rapid degradation through ubiquitination and proteasomal targeting. Growth factor withdrawal, as a model of cellular stress, stabilized RPRM protein levels. Together these data suggest that RPRM is transiently up-regulated at a posttranscriptional level in times of cellular stress to restrict cell survival, proliferation, and tumor formation. When RPRM is silenced as in human pituitary tumors, unrestrained growth and tumor progression may occur.

Immunonegative "Null Cell" Adenomas and Gonadotropin (Gn) Subunit (SUs) Immunopositive Adenomas Share Frequent Expression of Multiple Transcription Factors

2006 ◽  
Vol 17 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Yudo Ishii ◽  
Masanori Suzuki ◽  
Susumu Takekoshi ◽  
Noboru Egashira ◽  
Michio Yamazaki ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Null Cell ◽  
Null Cell Adenomas
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