Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer

Naren Gupta, Pamela M. Martin, Seiji Miyauchi, Sudha Ananth, Anne V. Herdman, Robert Martindale, Robert Podolsky, Vadivel Ganapathy

Research output: Contribution to journalArticle

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Abstract

Expression of Breast Cancer Resistance Protein (BCRP/ABCG2) in tumor cells is associated with resistance to multiple chemotherapeutic agents. BCRP also protects against phototoxicity by mediating the efflux of protoporphyrins from cells. However, chemotherapy and photodynamic therapy are effective treatment options for cancer. Furthermore, protoporphyrins are essential, in the form of heme, for the synthesis of nitric oxide, over-production of which is associated with cancer. This raises the question as to whether the expression of this transporter is altered in cancer. To address this question, we investigated the expression of BCRP in colorectal cancer and cervical cancer. Paired normal and cancer tissues from colectomy specimens were used for the analysis of BCRP mRNA by RT-PCR and Northern blot. BCRP was analyzed by immunohistochemistry/ immunofluorescence. Similar studies were also done with specimens of normal cervix and cancer cervix. A commercial dot blot was probed to quantify the expression of BCRP in paired normal and cancer cDNA samples from 154 patients with tumors in 19 different tissues. BCRP mRNA was present in normal colorectal tissue and showed a 6-fold decrease in cancer. BCRP was abundant in the normal colon and showed a decrease in colon cancer. The down-regulation of BCRP mRNA and protein was also evident in cervical cancer. There was also a decrease in BCRP mRNA in cancer in 12 of the 19 different tissues collected from 154 patients. These data show that cancer-associated down-regulation of BCRP is likely to be a common phenomenon in several tissues. Decreased expression of BCRP may have a role in tumorigenesis by allowing accumulation of genotoxins and over-production of nitric oxide.

Original languageEnglish (US)
Pages (from-to)571-577
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume343
Issue number2
DOIs
StatePublished - May 5 2006

Fingerprint

Uterine Cervical Neoplasms
Colorectal Neoplasms
Down-Regulation
Tissue
Messenger RNA
Protoporphyrins
Neoplasms
Tumors
Nitric Oxide
Photodynamic therapy
Chemotherapy
Mutagens
Heme
Proteins
Complementary DNA
Cells
Phototoxic Dermatitis
Colectomy
Photochemotherapy
Northern Blotting

Keywords

  • ABCG2 protein
  • ATP-binding cassette transporters
  • Breast Cancer Resistance Protein
  • Cervical cancer
  • Colorectal cancer
  • Drug resistance and cancer
  • iNOS
  • Protoporphyrins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Gupta, N., Martin, P. M., Miyauchi, S., Ananth, S., Herdman, A. V., Martindale, R., ... Ganapathy, V. (2006). Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. Biochemical and Biophysical Research Communications, 343(2), 571-577. https://doi.org/10.1016/j.bbrc.2006.02.172

Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. / Gupta, Naren; Martin, Pamela M.; Miyauchi, Seiji; Ananth, Sudha; Herdman, Anne V.; Martindale, Robert; Podolsky, Robert; Ganapathy, Vadivel.

In: Biochemical and Biophysical Research Communications, Vol. 343, No. 2, 05.05.2006, p. 571-577.

Research output: Contribution to journalArticle

Gupta, N, Martin, PM, Miyauchi, S, Ananth, S, Herdman, AV, Martindale, R, Podolsky, R & Ganapathy, V 2006, 'Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer', Biochemical and Biophysical Research Communications, vol. 343, no. 2, pp. 571-577. https://doi.org/10.1016/j.bbrc.2006.02.172
Gupta, Naren ; Martin, Pamela M. ; Miyauchi, Seiji ; Ananth, Sudha ; Herdman, Anne V. ; Martindale, Robert ; Podolsky, Robert ; Ganapathy, Vadivel. / Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 343, No. 2. pp. 571-577.
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