Publication: Extensive alteration in the expression profiles of TGFB pathway signaling components and TP53 is observed
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Date
2008
Authors
Seok-Hyung Kim ; Seung-Hyun Lee ; Yoon-La Choi ; Li-Hui Wang ; Cheol Keun Park ; Young Kee Shin
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Summary. Aims: The expression patterns of TGFB
signaling proteins, such as TGFB1/2, TGFBR1(ALK5),
TGFBR2, SMAD1/2/3, SMAD2/3, SMAD4, SMAD7,
and of downstream targets of TGFB signaling,
CDKN1A (p21CIP1), CDKN1B (p27KIP1), MYC,
CDC25A, TP53, and RELA (p65NF-kB) were
investigated in gastric carcinomas and other gastric
lesions. Methods and results: A total of 112 gastric
carcinomas, 37 dysplasias, 54 intestinal metaplasias, 29
chronic atrophic gastritis and 54 normal gastric
epithelium were analyzed by tissue microarray-based
immunohistochemical analysis. Extensive changes in
expression profiles of these proteins were observed.
Three types of expression patterns were observed along
the normal epithelium-atrophic gastritis-dysplasiacarcinoma sequence. (1) Expression of TGFB1/2,
TGFBR1, MYC, and TP53 continually increased along
this sequence. (2) Expression of SMAD4, CDKN1A,
SMAD1/2/3, SMAD2/3, and CDKN1B was enhanced in
dysplasia but decreased in carcinoma. (3) Expression of
TGFBR2, SMAD7, RELA, and CDC25A was enhanced
in dysplasia and the enhanced level was maintained in
carcinoma. In addition, we also evaluated the clinical
significance of the expression of TGFB signaling
proteins in gastric carcinoma. TGFB and MYC were
positively correlated with advanced stages, whereas
SMAD1/2/3 and SMAD4 were strongly associated with
earlier stages. Conclusions: The extensive change in
expression of TGFB signaling components is implicated
during tumorigenesis of gastric neoplasias.
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