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


METHODS
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.


CONCLUSIONS
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.
Reiske
Heinz
H
Functional Genetics, Inc., Gaithersburg, Maryland 20878, USA.
Sui
Baoquan
B
Ung-Medoff
Huong
H
Donahue
Robert
R
Li
Wu-Bo
WB
Goldblatt
Michael
M
Li
Limin
L
Kinch
Michael S
MS
D017302:Annexins / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002874:Chromosome Mapping; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015723:Gene Library; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D020123:Sirolimus / Q000494:pharmacology
D017302:Annexins; D000970:Antineoplastic Agents; D020123:Sirolimus