Role of the drug transporter ABCC3 in breast cancer chemoresistance

Sai A. Balaji, Nayanabhirama Udupa, Mallikarjuna Rao Chamallamudi, Vaijayanti Gupta, Annapoorni Rangarajan

Research output: Contribution to journalArticle

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Abstract

Increased expression of ABC-family of transporters is associated with chemotherapy failure. Although the drug transporters ABCG2, ABCB1 and ABCC1 have been majorly implicated in cancer drug resistance, recent studies have associated ABCC3 with multi drug resistance and poor clinical response. In this study, we have examined the expression of ABCC3 in breast cancers and studied its role in drug resistance and stemness of breast cancer cells in comparison with the more studied ABCC1. We observed that similar to ABCC1, the transcripts levels of ABCC3 was significantly high in breast cancers compared to adjacent normal tissue. Importantly, expression of both transporters was further increased in chemotherapy treated patient samples. Consistent with this, we observed that treatment of breast cancer cell lines with anti-cancer agents increased their mRNA levels of both ABCC1 and ABCC3. Further, similar to knockdown of ABCC1, knockdown of ABCC3 also significantly increased the retention of chemotherapeutic drugs in breast cancer cells and rendered them more chemo-sensitive. Interestingly, ABCC1 and ABCC3 knockdown cells also showed reduction in the expression of stemness genes, while ABCC3 knockdown additionally led to a reduction in the CD44high/CD24low breast cancer stem-like subpopulation. Consistent with this, their ability to form primary tumours was compromised. Importantly, down-modulation of ABCC3 rendered these cells increasingly susceptible to doxorubicin in xenograft mice models in vivo. Thus, our study highlights the importance of ABCC3 transporters in drug resistance to chemotherapy in the context of breast cancer. Further, these results suggest that combinatorial inhibition of these transporters together with standard chemotherapy can reduce therapy-induced resistance in breast cancer.

Original languageEnglish
Article numbere0155013
JournalPLoS One
Volume11
Issue number5
DOIs
Publication statusPublished - 01-05-2016

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breast neoplasms
transporters
Chemotherapy
Breast Neoplasms
drugs
Pharmaceutical Preparations
drug therapy
drug resistance
Cells
Drug Resistance
Drug Therapy
Heterografts
Neoplasms
Doxorubicin
neoplasms
doxorubicin
Aptitude
ATP-Binding Cassette Transporters
Tumors
multiple drug resistance

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Balaji, Sai A. ; Udupa, Nayanabhirama ; Chamallamudi, Mallikarjuna Rao ; Gupta, Vaijayanti ; Rangarajan, Annapoorni. / Role of the drug transporter ABCC3 in breast cancer chemoresistance. In: PLoS One. 2016 ; Vol. 11, No. 5.
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Role of the drug transporter ABCC3 in breast cancer chemoresistance. / Balaji, Sai A.; Udupa, Nayanabhirama; Chamallamudi, Mallikarjuna Rao; Gupta, Vaijayanti; Rangarajan, Annapoorni.

In: PLoS One, Vol. 11, No. 5, e0155013, 01.05.2016.

Research output: Contribution to journalArticle

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