Identification of annexin A13 as a regulator of chemotherapy resistance using random homozygous gene perturbation

Heinz Reiske, Baoquan Sui, Huong Ung-Medoff, Robert Donahue, Wu Bo Li, Michael Goldblatt, Limin Li, Michael S. Kinch

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

OBJECTIVE: To utilize a powerful new technology for target discovery, Random Homozygous Gene Perturbation (RHGP), and to identify novel targets that cause tumor cells to become chemoresistant. STUDY DESIGN: RHGP was used to identify and validate genetic changes that cause chemoresistance of tumor cells to Rapamycin. RESULTS: A series of targets was identified that allowed tumor cells to survive treatment with Rapamycin. We validated these targets and focused on Annexin A13, a target where decreased expression caused tumor cell insensitivity to Rapamycin. Ectopic overexpression of Annexin A13 was likewise sufficient to sensitize malignant breast cancer cells to treatment with Rapamycin. CONCLUSION: These findings expand our knowledge of mechanisms that allow tumor cell drug resistance and demonstrate the power of RHGP to identify novel targets and mechanisms.

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalAnalytical and Quantitative Cytology and Histology
Volume32
Issue number2
StatePublished - Apr 1 2010
Externally publishedYes

Keywords

  • Cancer
  • Drug resistance

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