Alterations in tropomyosin isoform expression in human transitional cell carcinoma of the urinary bladder.
Previous studies of transformed rodent fibroblasts have suggested that specific isoforms of the actin-binding protein tropomyosin (TM) could function as suppressors of transformation, but an analysis of TM expression in patient tumor tissue is limited. The purpose of our study was to characterize expression of the different TM isoforms in human transitional cell carcinoma of the urinary bladder by immunohistochemistry and Western blot analysis. We found that TM1 and TM2 protein levels were markedly reduced and showed >60% reduction in 61% and 55% of tumor samples, respectively. TM5, which was expressed at very low levels in normal bladder mucosa, exhibited aberrant expression in 91% of tumor specimens. The Western blot findings were confirmed by immunohistochemical analysis in a number of tumors. We then investigated the mechanism underlying TM expression deregulation, in the T24 human bladder cancer cell line. We showed that levels of TM1, TM2 and TM3 are reduced in T24 cells, but significantly upregulated by inhibition of the mitogen-activated protein kinase-signaling pathway. In addition, inhibition of this pathway was accompanied by restoration of stress fibers. Overall, changes in TM expression levels seem to be an early event during bladder carcinogenesis. We conclude that alterations in TM isoform expression may provide further insight into malignant transformation in transitional cell carcinomas of the bladder and may be a useful target for early detection strategies.
Pawlak
Geraldine
G
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
McGarvey
Terence W
TW
Nguyen
Trang B
TB
Tomaszewski
John E
JE
Puthiyaveettil
Raghunath
R
Malkowicz
S Bruce
SB
Helfman
David M
DM
D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D009092:Mucous Membrane / Q000378:metabolism; D020033:Protein Isoforms; D015398:Signal Transduction; D013997:Time Factors; D051348:Tropomodulin; D014335:Tropomyosin / Q000096:biosynthesis* / Q000737:chemistry*; D015854:Up-Regulation; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D004791:Enzyme Inhibitors; D020033:Protein Isoforms; C495833:TMOD2 protein, human; C495836:TMOD3 protein, human; D051348:Tropomodulin; D014335:Tropomyosin