Proteomic analysis of high-molecular-weight protein polymers in a doxorubicin-resistant breast-cancer cell line

Sung Soo Park, Dae Seok Kim, Kang Seo Park, Hye Jin Song, Soo Youl Kim

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)555-560
Number of pages6
JournalProteomics - Clinical Applications
Issue number6
StatePublished - Jun 2007
Externally publishedYes


  • Cross-linked proteins
  • Doxorubicin
  • MCF-7
  • Ribonucleoprotein A1
  • Transglutaminase 2

ASJC Scopus subject areas

  • Clinical Biochemistry


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