細胞激素對甲狀腺未分化癌再分化及細胞凋亡的影響
Other Title
The effects of cytokines on the differ entiation and apoptosis of anaplastic
thyroid cancer
thyroid cancer
Date Issued
2002
Date
2002
Author(s)
張天鈞
DOI
902314B002253
Abstract
Anaplastic thyroid cancer is almost
uniformly fatal. Microvilli are an important
three-dimensional (3-D) cytomorphological
feature of thyrocyte differentiation, as fewer
microvilli being seen in less differentiated
cancer. Differentiation therapies, such as
retinoic acid and somatostatin, have been
testd in differentiated thyroid cancer
experimental models, but not on anaplastic
thyroid cancer before. The aim of this study
was to elucidate whether TNF-α can induce
3-D cytomorphological differentiation of
anaplastic thyroid cancer cells, and, if so, to
investigate the mechanism involved.
Anaplastic thyroid cancer cells were treated
with TNF-α and examined for evidence of
cytomorphological differentiation using
electron microscopy. To study the
mechanism of differentiation,
immunoblotting was used to analyze I-κ B
proteins and electrophoretic mobility shift
assays to analyze NF-κ B activation. The
effect of NF-κ BSN50, a NF-κ B
translocation inhibitor, on cytomorphological
changes induced in anaplastic thyroid cancer
cells by TNF-α was also studied.
Meanwhile, levels of thyroglobulin and
vascular endothelial growth factor (VEGF)
secreted into the culture medium were also
measured. Our results showed that TNF-α
can induce activation of NF-κ B and that
the activation and translocation of NF-κ B into the nucleus is responsible for promoting
the 3-D cytomorphological differentiation of
anaplastic thyroid cancer cells, which could
be inhibited by the NF-κ B translocation
inhibitor, NF-κ B SN50. TNF-α also
induced increased thyroglobulin secretion
and reduced VEGF secretion by anaplastic
cancer cells. Our data suggest that TNF-α
can induce thyrocyte differentiation in
anaplastic thyroid cancer cells through NF-κ
B and that it merits investigation as
differentiation therapy for the treatment of
anaplastic thyroid cancer. We also found that
microvilli to be a useful marker for studying
thyrocyte differentiation in thyroid anaplastic
cancer cells.
Subjects
tumor necrosis factor α,
anaplastic thyroid carcinoma
anaplastic thyroid carcinoma
cytomorphology
nuclear factor kB
differentiation
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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