Apoptosis in Nontumorous and Neoplastic Human Pituitaries

Abstract

Analyses of apoptosis and of the apoptosis regulatory proteins Bcl-2, Bax, Bcl-X, and Bad were done in 95 nontumorous and neoplastic pituitary tissues by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL), immunohistochemistry, and Western blotting. The apoptotic index was relatively low in all groups but was at least fourfold higher in pituitary carcinomas compared with any other groups. Pituitaries from pregnant and postpartum women had a fivefold higher apoptotic index compared with matched controls from nonpregnant females. Preoperative treatment of adenomas with octreotide or dopamine agonists did not change the apoptotic index significantly. The lowest levels of Bcl-2, Bax, and Bcl-X expression were in pituitary carcinomas as detected by immunostaining. An immortalized human pituitary adenoma cell line, HP75, developed in our laboratory using a replication-defective recombinant human adenovirus with an early large T-antigen, had a much higher level of apoptosis than nontumorous and neoplastic pituitaries. Treatment with transforming growth factor (TGF)-beta1 and protein kinase C (PKC) inhibitors increased apoptosis in this cell line. Analysis of the Bcl-2 family of proteins after treatment with TGF-beta1 and PKC inhibitors showed a 20% to 30% decrease in Bcl-X in the treated groups compared with controls. These results, which represent the first study of apoptosis in pituitaries from pregnant and postpartum cases and in pituitary carcinomas, indicate that 1) the apoptotic rate is low in nontumorous and neoplastic pituitary tissues but is relatively higher in pituitary carcinomas, 2) there are alterations in the expression of the Bcl-2 family of proteins in pituitary neoplasms with a decrease in Bcl-2 expression in pituitary carcinomas that may contribute to pituitary tumor pathogenesis and/or proliferation, and 3) cultured pituitary tumor cells respond to TGF-beta1 and PKC inhibitors by undergoing apoptotic cell death.

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

“…Western blot of full thickness bladder samples showed a band at 26 kd ( Figure 6I), as previously reported, 23 and quantification, using Bcl-2/␤ actin ratios, showed a significant down-regulation (approximately 50%) of Bcl-2 protein in obstructed versus sham bladders (n ϭ 6 each group, P Ͻ 0.05). Bax immunohistochemistry revealed that this pro-death protein was also present within the cytoplasm of cells within all layers of the sham ( Figure 6, D and F) and obstructed ( Figure 6, G and H) fetal bladders at 105 days gestation; moreover, the staining intensity was subjectively increased in the obstructed versus sham detrusor SMC and lamina propria (eg, compare Figure 6G with 6D, and compare Figure 6H with 6F) and also appeared prominent within the luminal layers of the urothelium in bladders from both groups.…”

“…Bax immunohistochemistry revealed that this pro-death protein was also present within the cytoplasm of cells within all layers of the sham ( Figure 6, D and F) and obstructed ( Figure 6, G and H) fetal bladders at 105 days gestation; moreover, the staining intensity was subjectively increased in the obstructed versus sham detrusor SMC and lamina propria (eg, compare Figure 6G with 6D, and compare Figure 6H with 6F) and also appeared prominent within the luminal layers of the urothelium in bladders from both groups. Western blot of full thickness bladder samples showed a band at 22 kd ( Figure 6I), as previously reported, 23 and quantification, using Bax/␤ actin ratios, showed a significant up-regulation (approximately 200%) of Bax protein in obstructed versus sham bladders (n ϭ 6 each group, P Ͻ 0.001).…”

Poorly differentiated synovial sarcoma: A case report

“…Moreover, an inverse correlation between Bcl-2 expression and apoptotic events has been confirmed in vivo. 13,26 Chilosi 4 found that synovial sarcoma was Bcl-2 positive. Analogously, Nicholson 18 and Suster 25 found Bcl-2 positivity in 100% of synovial sarcomas.…”

Etiopatogênese Molecular dos Tumores Corticotróficos

“…Kontogeorgos e cols. (84), usando outra técnica, confirmou a presença de uma maior índice apoptótico nos tumores funcionantes, mas encontrou uma associação entre o acúmulo da proteína p53 intra-nuclear e um menor grau de apoptose. Kulig e cols.…”