Expression of ABCG2 in Human Liver Cancer Cell Lines and Its Related Functions_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

QIANG Guanghui ¹ , YU Decai ² , DING Xiwei ³ , JIANG Chunping. ²

1. Department of General Surgery，Gaochun People’s Hospital，Nanjing 211300，Jiangsu Province，China;;
2. Department of Hepatobiliary Surgery，Affiliated Drum Tower Hospital of Nanjing University Medical College，Nanjing 210008，Jiangsu Province，China;;
3. Nanjing University Medical College，Nanjing 210008，Jiangsu Province，China;

Corresponding author：

Keywords：

ABCG2; Liver cancer; Stem cell

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the expression of ATP-binding cassette superfamily G member 2 （ABCG2） in liver cancer cell lines and the relationship between ABCG2 expression and liver cancer drug resistance，and observe the difference of function between the ABCG2 positive cells and negative cells．
Methods 　The expressions of ABCG2 in four liver cancer cell lines （PLC/PRF/5，7402，7701，and 7721） were detected by flow cytometry．IC50 of 5-fluorouracil （5-FU） and adriamycin were calculated．The expression of the ABCG2 in the 7721 cell lines was observed by immunofluorescence staining．The ABCG2 positive and negative cells were selected by the axenic flow sorting method，the difference of function between the ABCG2 positive cells and negative cells was compared．
Results 　The positive expression rate of ABCG2 in the cell line 7721 was highest among four liver cancer cell lines（P＜0.05），and the ABCG2 positive and negative cells had clear bimodal．IC50 of 5-FU and adriamycin to the cell line 7721 were higher than those of the other three cell lines （P＜0.05） except for 5-FU to the cell line 7701．There was no difference in cell proliferation between ABCG2 positive cells and negative cells．Cell cycle analysis showed that the ABCG2 positive cells had more quiescent cells as compared with the negative cells（P＜0.05）．
Conclusions 　ABCG2 expresses in a variety human liver cancer cell lines，ABCG2 positive cells have some stem cell features like drug resistance and more quiescent cells comparing with the negative cells．

Citation： QIANG Guanghui,YU Decai,DING Xiwei,JIANG Chunping.. Expression of ABCG2 in Human Liver Cancer Cell Lines and Its Related Functions. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(2): 146-150. doi: Copy

1.	Robey RW，Polgar O，Deeken J，et al．ABCG2：determining its relevance in clinical drug resistance[J]．Cancer Metastasis Rev， 2007，26(1)：39-57．.
2.	Zhou S，Schuetz JD，Bunting KD，et al．The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype[J]．Nat Med，2001，7(9)：1028-1034．.
3.	Ding XW，Wu JH，Jiang CP．ABCG2：a potential marker of stem cells and novel target in stem cell and cancer therapy[J]． Life Sci，2010，86(17-18)：631-637．.
4.	Ross DD，Nakanishi T．Impact of breast cancer resistance protein on cancer treatment outcomes[J]．Methods Mol Biol，2010， 596：251-290．.
5.	Dean M，Fojo T，Bates S．Tumour stem cells and drug resistance[J]．Nat Rev Cancer，2005，5(4)：275-284．.
6.	徐叔云，卞如濂，陈修．药理实验方法[ M]．第 2版．北京：人民卫生出版社，1991：731．.
7.	刘宝瑞，王婷婷，钱晓萍．原发性肝癌分子靶向治疗研究进展[ J]．世界华人消化杂志，2009，17(10)：993-997．.
8.	Li F，Tiede B，Massagué J，et al．Beyond tumorigenesis：cancer stem cells in metastasis[J]．Cell Res，2007，17(1)：3-14．.
9.	Visvader JE，Lindeman GJ．Cancer stem cells in solid tumours： accumulating evidence and unresolved questions[J]．Nat Rev Cancer，2008，8(10)：755-768．.
10.	Chiba T，Kita K，Zheng YW，et al．Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J]．Hepatology，2006，44(1)：240-251．.
11.	Kim M，Turnquist H，Jackson J，et al．The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst33342 and is overexpressed in hematopoietic stem cells[J]．Clin Cancer Res，2002，8(1)：22-28．.
12.	Scharenberg CW，Harkey MA,Torok-Storb B．The ABCG2 transporter is an efficient Hoechst33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors[J]．Blood，2002，99(2)：507-512．.
13.	Challen GA，Little MH．A side order of stem cells：the SP phenotype[J]．Stem Cells，2006，24(1)：3-12．.
14.	Ahmed F，Arseni N，Glimm H，et al．Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors[J]．Stem Cells，2008，26(3)：810-818．.
15.	Bhattacharya S，Das A，Mallya K，et al．Maintenance of retinal stem cells by Abcg2 is regulated by notch signaling[J]．J Cell Sci，2007，120(Pt 15)：2652-2662．.
16.	Diestra JE，Scheffer GL，Catala I，et al．Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material[J]．J Pathol，2002， 198(2)：213-219．.
17.	Chen Z，Liu F，Ren Q，et al．Suppression of ABCG2 inhibits cancer cell proliferation[J]．Int J Cancer，2010，126(4)：841851．.
18.	Vlaming ML，Lagas JS，Schinkel AH．Physiological and pharmacological roles of ABCG2 (BCRP)：Recent findings in Abcg2 knockout mice[J]．Adv Drug Deliv Rev，2009，61(1)：14-25．.
19.	Polgar O，Robey RW，Bates SE．ABCG2：structure，function and role in drug response[J]．Expert Opin Drug Metab Toxicol， 2008，4(1)：1-15．.
20.	Rocchi E，Khodjakov A，Volk EL，et al．The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane[J]．Biochem Biophys Res Commun， 2000，271(1)：42-46．.
21.	Zen Y，Fujii T，Yoshikawa S，et al．Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma[J]． Am J Pathol，2007，170(5)：1750-1762．.

1. Robey RW，Polgar O，Deeken J，et al．ABCG2：determining its relevance in clinical drug resistance[J]．Cancer Metastasis Rev， 2007，26(1)：39-57．.
2. Zhou S，Schuetz JD，Bunting KD，et al．The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype[J]．Nat Med，2001，7(9)：1028-1034．.
3. Ding XW，Wu JH，Jiang CP．ABCG2：a potential marker of stem cells and novel target in stem cell and cancer therapy[J]． Life Sci，2010，86(17-18)：631-637．.
4. Ross DD，Nakanishi T．Impact of breast cancer resistance protein on cancer treatment outcomes[J]．Methods Mol Biol，2010， 596：251-290．.
5. Dean M，Fojo T，Bates S．Tumour stem cells and drug resistance[J]．Nat Rev Cancer，2005，5(4)：275-284．.
6. 徐叔云，卞如濂，陈修．药理实验方法[ M]．第 2版．北京：人民卫生出版社，1991：731．.
7. 刘宝瑞，王婷婷，钱晓萍．原发性肝癌分子靶向治疗研究进展[ J]．世界华人消化杂志，2009，17(10)：993-997．.
8. Li F，Tiede B，Massagué J，et al．Beyond tumorigenesis：cancer stem cells in metastasis[J]．Cell Res，2007，17(1)：3-14．.
9. Visvader JE，Lindeman GJ．Cancer stem cells in solid tumours： accumulating evidence and unresolved questions[J]．Nat Rev Cancer，2008，8(10)：755-768．.
10. Chiba T，Kita K，Zheng YW，et al．Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties[J]．Hepatology，2006，44(1)：240-251．.
11. Kim M，Turnquist H，Jackson J，et al．The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst33342 and is overexpressed in hematopoietic stem cells[J]．Clin Cancer Res，2002，8(1)：22-28．.
12. Scharenberg CW，Harkey MA,Torok-Storb B．The ABCG2 transporter is an efficient Hoechst33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors[J]．Blood，2002，99(2)：507-512．.
13. Challen GA，Little MH．A side order of stem cells：the SP phenotype[J]．Stem Cells，2006，24(1)：3-12．.
14. Ahmed F，Arseni N，Glimm H，et al．Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors[J]．Stem Cells，2008，26(3)：810-818．.
15. Bhattacharya S，Das A，Mallya K，et al．Maintenance of retinal stem cells by Abcg2 is regulated by notch signaling[J]．J Cell Sci，2007，120(Pt 15)：2652-2662．.
16. Diestra JE，Scheffer GL，Catala I，et al．Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material[J]．J Pathol，2002， 198(2)：213-219．.
17. Chen Z，Liu F，Ren Q，et al．Suppression of ABCG2 inhibits cancer cell proliferation[J]．Int J Cancer，2010，126(4)：841851．.
18. Vlaming ML，Lagas JS，Schinkel AH．Physiological and pharmacological roles of ABCG2 (BCRP)：Recent findings in Abcg2 knockout mice[J]．Adv Drug Deliv Rev，2009，61(1)：14-25．.
19. Polgar O，Robey RW，Bates SE．ABCG2：structure，function and role in drug response[J]．Expert Opin Drug Metab Toxicol， 2008，4(1)：1-15．.
20. Rocchi E，Khodjakov A，Volk EL，et al．The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane[J]．Biochem Biophys Res Commun， 2000，271(1)：42-46．.
21. Zen Y，Fujii T，Yoshikawa S，et al．Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma[J]． Am J Pathol，2007，170(5)：1750-1762．.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of ABCG2 in Human Liver Cancer Cell Lines and Its Related Functions

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