38. Akt-1 Inhibition Is Important for Suppression of Neuroendocrine Hormone Secretion in Carcinoid Tumor Cells

2008 ◽  
Vol 144 (2) ◽  
pp. 192
Author(s):  
Susan Pitt ◽  
Herbert Chen ◽  
Muthusamy Kunnimalaiyaan
Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
TP Wyche ◽  
R Jaskula-Sztul ◽  
A Dammalapati ◽  
H Cho ◽  
G Kwon ◽  
...  
Keyword(s):  

2006 ◽  
Vol 13 (3) ◽  
pp. 955-962 ◽  
Author(s):  
E Ferrante ◽  
C Pellegrini ◽  
S Bondioni ◽  
E Peverelli ◽  
M Locatelli ◽  
...  

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160 ± 20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172 ± 25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.


2008 ◽  
Vol 199 (2) ◽  
pp. 177-189 ◽  
Author(s):  
Marta Labeur ◽  
Damian Refojo ◽  
Barbara Wölfel ◽  
Johanna Stalla ◽  
Vivian Vargas ◽  
...  

Interferon-γ (IFNG) is a cytokine that exerts potent antiproliferative and tumoricidal effects in a variety of cancers. Moreover, IFNG modulates normal pituitary hormone secretion, and was shown to inhibit the expression of the ACTH precursor POMC in murine ACTH-secreting AtT-2010/21/2008 tumor cells. We have studied the functional role of IFNG on pituitary tumor cells, focusing on the involvement of IFNG in the molecular events leading to the control of POMC transcriptional repression. Herein, it is shown that IFNG inhibits AtT-20 tumor cell proliferation without inducing apoptosis. Unexpectedly, an activated janus kinases–signal transducer and activator of transcription (JAK–STAT1) cascade is required for IFNG inhibitory action on POMC promoter activity. Factor-kappa B (NF-κB) is necessary for the inhibitory action of IFNG on Pomc transcription, since loss of NF-κB activity with IκB super-repressor abolishes this effect. In addition, 1 and 2 IFNG receptor immunoreactivity was detected in human corticotropinoma cells. Interestingly, IFNG inhibits ACTH production from these cells in primary cell culture, without affecting basal ACTH biosynthesis in normal non-tumoral pituitary cells. In conclusion, our data show for the first time that POMC transcription can be negatively regulated by a JAK–STAT1 and NF-κB-dependent pathway.


2012 ◽  
Vol 172 (2) ◽  
pp. 237 ◽  
Author(s):  
J.A. Sohn ◽  
B. Zarebczan ◽  
T.P. Wyche ◽  
T.S. Bugni ◽  
M. Kunnimalaiyaan ◽  
...  
Keyword(s):  

1987 ◽  
Vol 42 (2) ◽  
pp. 141-146 ◽  
Author(s):  
K.O. Grönstad ◽  
O. Nilsson ◽  
A. Dahlström ◽  
G. Skolnik ◽  
H. Ahlman

Cancer ◽  
1986 ◽  
Vol 58 (3) ◽  
pp. 676-684 ◽  
Author(s):  
Ola Nilsson ◽  
Håkan Ahlman ◽  
Lars E. Ericson ◽  
Gabor Skolnik ◽  
Annica Dahlström
Keyword(s):  

2005 ◽  
Vol 90 (7) ◽  
pp. 4350-4356 ◽  
Author(s):  
Eric K. Nakakura ◽  
Virote R. Sriuranpong ◽  
Muthusamy Kunnimalaiyaan ◽  
Edward C. Hsiao ◽  
Kornel E. Schuebel ◽  
...  

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