MTDH mediates estrogen-independent growth and tamoxifen resistance by down-regulating PTEN in MCF-7 breast cancer cells.
BACKGROUND
About 70% of human breast cancers express estrogen receptor α (ERα) and in this kind of breast cancer estrogen plays an important role. Estrogen independent growth has been reported to promote resistance to one of the selective estrogen receptor modulators (SERMs) tamoxifen which is clinically the first line treatment for patients with ERα-positive breast cancer. The resistance of tamoxifen is a major problem in the clinical management of breast cancer.


METHODS
We used MCF-7 cells with ectopic expression of MDTH in this study. MTT, clone formation and tumor formation in nude mice methods were utilized to confirm the role of MTDH in estrogen-independent growth and tamoxifen resistance. Flow cytometry, western blot and siRNA were used to study the detailed mechanisms.


RESULTS
We found that MTDH could mediate estrogen-independent growth and induce resistance to tamoxifen in ERα-positive breast cancer cells. MTDH could reduce the expression of PTEN, up-regulate AKT and BCL2 and inhibit the apoptosis induced by tamoxifen.


CONCLUSIONS
Our study indicated that MTDH was a candidate marker to predict the clinical efficacy of tamoxifen and targeting MTDH would overcome the resistance to tamoxifen in breast cancer cells.
Department of Oncology, Qilu Hospital, Shandong University, Jinan, P.R. China.
Chunyuan
C
Xu
Xiaoli
X
Kong
Haiji
H
Wang
Ning
N
Zhang
Xiangnan
X
Kong
Xia
X
Ding
Xiaoyan
X
Li
Qifeng
Q
Yang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000378:metabolism; D016601:RNA-Binding Proteins; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D004967:Estrogens; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D013629:Tamoxifen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human