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Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
07:55

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma

Published on: April 11, 2018

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

Yoshinao Oda1, Tsuyoshi Saito, Naomi Tateishi

  • 1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. oda@surgpath.med.kyushu-u.ac.jp

International Journal of Cancer
|December 21, 2004
PubMed

Insights

Multidrug resistance (MDR) proteins like MDR1 and MRP3 are highly expressed in malignant peripheral nerve sheath tumors, contributing to poor drug response. P-glycoprotein (P-gp) expression correlates with advanced soft tissue sarcoma stages and tumor size.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Multidrug resistance (MDR) in cancers is often mediated by ATP-binding cassette (ABC) transporters.
  • Expression of MDR-related proteins like P-glycoprotein (P-gp) and MDR-associated proteins (MRPs) in soft tissue sarcomas is not fully understood.
  • Understanding these mechanisms is crucial for improving cancer treatment efficacy.

Purpose of the Study:

  • To investigate the mRNA and protein expression levels of MDR1, MRP1, MRP2, and MRP3 in soft tissue sarcomas.
  • To correlate ABC transporter expression with clinicopathologic parameters and proliferation.
  • To explore the role of p53 in regulating MDR1 expression.

Main Methods:

  • Quantitative reverse transcriptase-PCR (RT-PCR) for intrinsic mRNA levels of MDR1, MRP1, MRP2, and MRP3.
  • Immunohistochemistry for protein expression of P-gp, MRP1, MRP2, MRP3, and p53.
  • Comparison of mRNA and protein expression levels with clinicopathologic data and MIB-1 labeling index.

Main Results:

  • Malignant peripheral nerve sheath tumors (MPNST) exhibited significantly higher MDR1 and MRP3 mRNA levels compared to other sarcoma types.
  • A strong correlation was observed between RT-PCR and immunohistochemical methods for assessing ABC transporter expression.
  • P-gp expression was linked to larger tumor size and higher AJCC stage (III/IV).
  • Nuclear p53 expression was associated with increased MDR1 mRNA levels.

Conclusions:

  • MDR1/P-gp expression plays a significant role in soft tissue sarcoma progression.
  • p53 may act as a regulator of MDR1 gene expression.
  • Elevated MDR1 and MRP3 mRNA in MPNST likely contributes to their resistance to chemotherapy.

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