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Proteomic analysis of high‐molecular‐weight protein polymers in a doxorubicin‐resistant breast‐cancer cell line
Author(s) -
Park SungSoo,
Kim DaeSeok,
Park KangSeo,
Song HyeJin,
Kim SooYoul
Publication year - 2007
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200700122
Subject(s) - doxorubicin , tissue transglutaminase , cell culture , cancer cell , biology , biochemistry , chemistry , cancer , cancer research , microbiology and biotechnology , enzyme , genetics , chemotherapy
We recently reported that increased transglutaminase 2 (TGase 2) expression correlates with increased resistance to the cancer drug doxorubicin in breast‐cancer cell lines. Interestingly, high‐molecular‐weight (HMW) proteins also increased with increased TGase 2 expression in the drug‐resistant cell lines. TGase 2 is likely to be responsible for the formation of HMW proteins, because TGase 2 catalyzes cross‐linking between proteins. Although the role of the HMW proteins is unclear, we demonstrated that TGase 2 inhibition increases drug sensitivity in breast‐cancer cells. Herein we find that TGase 2 inhibition by cystamine dramatically reduces the level of HMW proteins. Identification of the HMW proteins may suggest the mechanism of cancer drug resistance associated with aberrant TGase 2 function. To explore the identities of HMW proteins, we performed in‐gel tryptic digestions of unresolved HMW proteins and analyzed the resulting peptides using LC‐MALDI‐MS/MS. Most of the identified proteins were associated with gene regulation, such as polyadenylate‐binding proteins, translation initiation factors, and ribonucleoproteins. This finding suggests that TGase 2 may participate in gene regulation, in addition to its role in cell adhesion.