Expression and function of ABCG2 in head and neck squamous cell carcinoma and cell lines

Abstract

Abstract. Overexpression of breast cancer resistance protein, the ATP-binding cassette, subfamily G, member2 (BCRP/ABCG2), confers multidrug resistance to tumor cells and often limits the efficacy of chemotherapy. The aim of this study was to investigate the expression and functional activity of ABCG2 in head and neck squamous cell carcinoma (HNSCC) and corresponding cell lines. Immunohistochemistry was performed to investigate the presence of the ABCG2 transporter in HNSCC tissues. Expression of ABCG2 in the Hep-2, Hep-2T, CNE and FaDu cell lines was analyzed by real-time quantitative reverse transcription-polymerase chain reaction and Western blotting at the levels of messenger RNA (mRNA) and protein, respectively. The drug sensitivity of the above four cell lines to mitoxantrone was detected using MTT, and the drug accumulation of mitoxantrone was analyzed by flow cytometry. Positive expression of ABCG2 was detected in 52.04% of the laryngeal cancer samples from 98 patients, in 65% of the 40 hypopharyngeal cancer samples and in 58.82% of the 34 nasopharyngeal cancer samples. The level of expression was found to be correlated with tumor TNM stage (P<0.05) and lymph node metastasis (P<0.01). All four HNSCC cell lines expressed ABCG2 at the mRNA and protein levels. The levels of ABCG2 expression in the four cell lines were significantly correlated with the function and sensitivity to mitoxantrone. The addition of fumitremorgin C at a concentration of 5 µM to mitoxantrone treatment caused a varied increase in mitoxantrone accumulation of 1.09-fold, 1.33-fold (P<0.01), 1.4-fold (P<0.01) and 1-fold in the Hep-2, Hep-2T, CNE and FaDu cells, respectively. Expression of ABCG2 varied among the different types of carcinoma tissues and each HNSCC cell line, and it induced multidrug resistance and separation of cancer stem cells attributing to its efflux pump function. Thus, ABCG2 expression may be an unfavorable prognostic factor for HNSCC. Due to the negligible expression and function of ABCG2, we suggest that the FaDu cell line is suitable to be a negative control in studies involving HNSCC. Taken together, ABCG2 is a promising universal biomarker of cancer stem cells and a target gene for HNSCC chemotherapy.

Expression of the cancer stem cell markers CD44v6 and ABCG2 in tongue cancer: Effect of neoadjuvant chemotherapy on local recurrence

“…Elevated expression of ABCG2 has been observed in a number of putative CSCs from various cancers (24,34,35). AGCG2 is a well-known marker useful for identifying and isolating CSCs (22)(23)(24)34,35,47). In our study, ABCG2 expression was 14.6% in OTSCC patients, similar to the 12.4% in esophageal squamous cell carcinoma (35).…”

Current cancer stem cell biomarkers in laryngeal cancer

“…ABCG2 is known to participate in chemoresistance and acquisition of stem cell features of tumor cells and its upregulation has been demonstrated in various cancer types [59]. Side population cells with CSCs features isolated from the laryngeal carcinoma cell line as well as primary laryngeal carcinoma cells [60] and CD133+ larynx CSCs isolated from freshly resected laryngeal tumor specimens [21] had significantly higher levels of ABCG2.…”

ABCG2 gene amplification and expression in esophageal cancer cells with acquired adriamycin resistance

“…This MDR is caused by several mechanisms, including increased drug efflux (1)(2)(3)(4)(5)(6)(7)(8), enhanced drug detoxification, alterations of targets, and modification of DNA damage repair systems (9)(10)(11) and apoptosis pathways (12). The drug efflux effect is mediated by the enhanced expression of one or more ATP-binding cassette (ABC) transporters (2,(13)(14)(15). One of these ABC transporters is breast cancer resistant protein (BCRP), which is encoded by the ABCG2 gene (16).…”