Differential proteome analysis of colon carcinoma cell line SW480 after reconstitution of the tumour suppressor Smad4.
The tumour suppressor gene Smad4 is frequently inactivated in gastrointestinal carcinomas. Smad4 plays a pivotal role in transducing signals of the transforming growth factor-beta (TGF-beta) superfamily of proteins. Inactivation of Smad4 seems to occur late during tumour progression when tumours acquire invasive and metastatic properties. Identification of proteins directly or indirectly regulated by Smad4 would, therefore, ease the future design of new diagnostic and therapeutic strategies for gastrointestinal carcinoma. We have used human colon carcinoma cell line SW480 stably transfected with Smad4 as an in-vitro model system to identify Smad4-regulated proteins by applying two-dimensional gel electrophoresis (2DE) then MALDI-PMF/PFF-MS. We identified a total of 47 protein species with a Smad4-dependent expression. From the functions of the candidate proteins we obtained new insights into Smad4's participation in processes, for example apoptosis, differentiation, and proliferation.
Stühler
Kai
K
Medizinisches Proteom-Center, Ruhr-University Bochum, ZKF E 1.43, Universitätsstrasse 150, 44801, Bochum, Germany. kai.stuehler@ruhr-uni-bochum.de
Köper
Katharina
K
Pfeiffer
Kathy
K
Tagariello
Andreas
A
Souquet
Manfred
M
Schwarte-Waldhoff
Irmgard
I
Hahn
Stephan A
SA
Schmiegel
Wolff
W
Meyer
Helmut E
HE
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D053535:Keratin-13 / Q000737:chemistry; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D051901:Smad4 Protein / Q000737:chemistry / Q000378:metabolism*
C507426:KRT13 protein, human; D053535:Keratin-13; D020033:Protein Isoforms; D020543:Proteome; C497796:SMAD4 protein, human; D051901:Smad4 Protein