Increased expression of multidrug resistance-associated genes after chemotherapy in pediatric solid malignancies.

Abstract

BACKGROUND/PURPOSE:

The overexpression of multidrug resistance (MDR)-associated genes in primary untreated tumors has been proven to be associated with worse prognosis in various pediatric malignancies. This study compared the expression of 3 MDR-associated genes, MDR1, MDR-associated protein 1 (MRP1), and lung resistance-related protein (LRP), in pediatric tumors before and after chemotherapy to elucidate the mechanism of MDR during chemotherapy.

METHODS:

Surgical specimens of both primary and chemotherapy-treated tumors were obtained from 24 patients with pediatric malignancies (neuroblastoma [NB] 8; hepatoblastoma [HB] 8; Wilms tumor [WT] 4; rhabdomyosarcoma [RB] 4). The expression of MDR1, MRP1, and LRP was evaluated using the immunohistochemical staining.

RESULTS:

In primary tumors, MDR1 expression was observed in 6 NBs, 8 HBs, 3 WTs, and 3 RBs. MRP1 expression was observed in 3 NBs and 1 HB. LRP expression was not detected in any of the primary tumors. After chemotherapy, MDR1 expression was observed to increase in 5 NBs, 4 HBs, 2 WTs, and 3 RBs. MRP1 expression was newly observed or increased in 7 NBs, 4 HBs, and 3 RBs. LRP expression was newly observed in 3 HBs and 2 WTs.

CONCLUSIONS:

These results indicate that these 3 MDR-associated genes were upregulated after chemotherapy in various pediatric malignancies. These findings may be useful to understand the mechanism of drug resistance in pediatric malignancies.

• Authors: Takaharu Oue, Akihiro Yoneda, Shuichiro Uehara, Hiroaki Yamanaka, Masahiro Fukuzawa
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 44 Issue 2 Pg. 377-80 (Feb 2009) ISSN: 1531-5037 [Electronic] United States
• PMID: 19231538 (Publication Type: Comparative Study, Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Multidrug Resistance-Associated Proteins
• Vault Ribonucleoprotein Particles
• major vault protein
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis)
• Adolescent
• Child
• Child, Preschool
• Drug Resistance, Neoplasm (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Genes, MDR (genetics)
• Humans
• Infant
• Male
• Multidrug Resistance-Associated Proteins (biosynthesis)
• Neoplasms (drug therapy, genetics, metabolism)
• Vault Ribonucleoprotein Particles (biosynthesis)