E. Kulig et al., Apoptosis in nontumorous and neoplastic human pituitaries - Expression of the Bcl-2 family of proteins, AM J PATH, 154(3), 1999, pp. 767-774
Citations number
38
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Analyses of apoptosis and of the apoptosis regulatory proteins Bcl-2, Bar,
Bcl-X, and Bad were done In 95 nontumorous and neoplastic pituitary tissues
by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (T
UNEL), 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 po
stpartum 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 signific
antly. The lowest levels of Bcl-2, Bar, and Bcl-X expression were in pituit
ary carcinomas as detected by immunostaining, An immortalized human pituita
ry 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 pituitarie
s. Treatment with transforming growth factor (TGF)-beta 1 and protein kinas
e C (PKC) inhibitors increased apoptosis in this cell line. Analysis of the
Bcl-2 family of proteins after treatment with TGF-beta 1 and PKC inhibitor
s 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 p
ituitaries from pregnant and postpartum cases and in pituitary carcinomas,
indicate that 1) the apoptotic rate is low in nontumorous and neoplastic pi
tuitary tissues but is relatively higher in pituitary carcinomas, 2) there
are alterations in the expression of the Bcl-2 family of proteins in pituit
ary neoplasms with a decrease in Bcl-2 expression In pituitary carcinomas t
hat may contribute to pituitary tumor pathogenesis and/or proliferation, an
d 3) cultured pituitary tumor cells respond to TGF-beta 1 and PKC inhibitor
s by undergoing apoptotic cell death.