TLK1B is elevated with eIF4E overexpression in breast cancer

Kathryn S. Norton, Derek McClusky, Siddhartha Sen, Herbert Yu, Carol Meschonat, Arrigo Debenedetti, Benjamin D.L. Li

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Introduction. The overexpression of eukaryotic initiation factor 4E (eIF4E), a critical component of the "RNA helicase" necessary for the initiation of protein synthesis of mRNAs with long 5′ prime untranslated regions (5′UTRs), can result in malignant transformation. In a prospective study on breast cancer outcome of women with stage I to III disease, eIF4E overexpression was an independent predictor of cancer recurrence (RR = 7.3, CI = 1.58-33.9). Dysregulation of Tousled-like kinase 1B (TLK1B), a threonine kinase with a highly conserved gene sequence, has been linked to defects in cell division and DNA replication. In cell lines, TLK1B overexpression has been recently associated with resistance to radiation. The 5′UTR of TLK1B is long (1088 nt) and the structure is complex. Our hypothesis is that TLK1B elevation is correlated with the overexpression of eIF4E in human breast carcinoma. Materials and methods. Eighty-seven patients with invasive breast cancer and 11 patients with benign breast disease were accrued prospectively. Clinical data collected include age, race, stage, grade of tumor, ER, and PR status. TLK1B and eIF4E levels were quantified by Western blot analysis. Statistical analysis was performed using Spearman correlation, paired and unpaired t test, and multivariate analysis. Results. In the 87 cancer specimens from patients with breast carcinoma, eIF4E level was elevated by a mean of 9.5-fold (range = 1.8-48.4), and TLK1B was elevated by a mean of 9.4-fold (range = 1.0-58.0) when compared to the 11 specimens from noncancer patients. Multivariate analysis performed demonstrates the degree of eIF4E overexpression is independent of age, race, tumor grade, and ER or PR status of the tumor. Similarly, the degree of TLK1B elevation is independent of age, tumor grade, and ER or PR status of the tumor. Using the Spearman correlation, the degree of TLK1B elevation was strongly correlated with the degree of eIF4E overexpression (r = 0.39, P = 0.001). Conclusions. Both eIF4E and TLK1B are elevated in breast cancer specimens but not in benign breast specimens from noncancer patients. The degree of TLK1B elevation is correlated with the degree of IF4E overexpression. Both eIF4E and TLK1B overexpression are independent of tumor grade, tumor stage, and ER and PR status.

Original languageEnglish (US)
Pages (from-to)98-103
Number of pages6
JournalJournal of Surgical Research
Volume116
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Bibliographical note

Funding Information:
This manuscript was presented in part at the 36th Annual Meeting of the Association for Academic Surgery in Boston, MA. This work was funded in part by NIH Grant CA 79082 and Grant BCTR0100512 from the Susan G. Komen foundation.

Keywords

  • Breast cancer
  • TLK1B
  • Threonine kinase
  • Translation control
  • eIF4E

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