ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcomas

Yoshinao Oda, Tsuyoshi Saito, Naomi Tateishi, Yoshihiro Ohishi, Sadafumi Tamiya, Hidetaka Yamamoto, Ryohei Yokoyama, Takeshi Uchiumi, Yukihide Iwamoto, Michihiko Kuwano, Masazumi Tsuneyoshi

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29 Citations (Scopus)

Abstract

The phenomenon of multidrug resistance (MDR) in various malignant neoplasms has been reported as being caused by one or multiple expressions of ATP-binding cassette (ABC) superfamily protein, including P-glycoprotein/multidrug resistance (MDR) 1 and the MDR protein (MRP) family. However, their expression levels and distribution within soft tissue sarcomas remain controversial. In 86 cases of surgically resected soft tissue sarcoma, intrinsic mRNA levels of MDR1, MRP1, MRP2 and MRP3 were assessed using a quantitative reverse transcriptase-PCR (RT-PCR) method. Moreover, immunohistochemical protein expressions of P-glycoprotein (P-gp), MRP1, MRP2, MRP3 and p53 protein were evaluated in concordant paraffin-embedded material. The mRNA expression and immunohistochemical expression of ABC superfamily transporters were compared to clinicopathologic parameters and proliferative activities as evaluated by the MIB-1-labeling index (LI). Among the various histologic types, malignant peripheral nerve sheath tumor (MPNST) showed significantly high levels of MDR1 (p=0.017) and MRP3 (p=0.0384) mRNA expression, compared to the other tumor types. When the immunohistochemical method was compared to the RT-PCR technique to assess ABC transported expression at the protein and mRNA levels, a significantly close relationship was found between the 2 methods (p<0.05). P-gp expression was significantly correlated with large tumor size (≥5 cm, p=0.041) and high AJCC stage (stages III and IV) (p=0.0365). Furthermore, cases with nuclear expression of p53 revealed significantly higher levels of MDR1 mRNA expression, compared to those with negative immunoreaction for p53 (p=0.0328). Our results suggest that MDR1/P-gp expression may have an important role to play in tumor progression in the cases of soft tissue sarcoma, and p53 may be one of the active regulators of the MDR1 transcript. In addition, the high levels of both MDR1 and MRP3 mRNA expression in MPNST may help to explain the poor response of this tumor to anticancer-drugs.

Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalInternational Journal of Cancer
Volume114
Issue number6
DOIs
Publication statusPublished - May 10 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Oda, Y., Saito, T., Tateishi, N., Ohishi, Y., Tamiya, S., Yamamoto, H., Yokoyama, R., Uchiumi, T., Iwamoto, Y., Kuwano, M., & Tsuneyoshi, M. (2005). ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcomas. International Journal of Cancer, 114(6), 854-862. https://doi.org/10.1002/ijc.20589