Abstract | BACKGROUND:
Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer. RESULTS: Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo. CONCLUSION:
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Authors | Yuan-Yuan Chen, Zhi-Zhen Li, Yuan-Yuan Ye, Feng Xu, Rui-Jie Niu, Hong-Chen Zhang, Yi-Jian Zhang, Ying-Bin Liu, Bao-San Han |
Journal | BMC molecular biology
(BMC Mol Biol)
Vol. 17
Pg. 6
(Mar 02 2016)
ISSN: 1471-2199 [Electronic] England |
PMID | 26935744
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- SALL4 protein, human
- Transcription Factors
- Doxorubicin
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Topics |
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Cell Cycle Checkpoints
(drug effects, genetics)
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
(drug effects, genetics)
- Disease Models, Animal
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
(genetics)
- Female
- Gene Expression
- Gene Knockdown Techniques
- Gene Silencing
- Humans
- Inhibitory Concentration 50
- MCF-7 Cells
- Mice
- Transcription Factors
(genetics)
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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