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TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line

Z Duan1, A J Feller, H C Toh

  • 1Masssachusetts General Hospital, Cox 640, Department of Hematology/Oncology, 100 Blossom Street, Boston, MA 02114, USA.

Gene
|March 30, 1999
PubMed

Insights

A novel gene, Taxol Resistance Associated Gene-3 (TRAG-3), was identified in taxol-resistant ovarian cancer cells. TRAG-3 overexpression correlates with chemotherapy resistance and neoplastic phenotypes across various cancer types.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Mechanisms of taxol resistance in cancer are not fully understood.
  • Drug resistance often involves multiple molecular changes.
  • Identifying novel genes associated with resistance can improve therapeutic strategies.

Purpose of the Study:

  • To identify molecular changes associated with taxol resistance.
  • To characterize a newly discovered gene, TRAG-3, in the context of drug resistance.
  • To investigate the expression pattern of TRAG-3 in various cancer cell lines and normal tissues.

Main Methods:

  • Establishment of a taxol-resistant ovarian cancer cell line (SKOV-3TR) from a parental line (SKOV-3).
  • Differential display to identify differentially expressed genes.
  • Nucleotide sequencing of TRAG-3 cDNA and genomic analysis.
  • Northern blot analysis to assess TRAG-3 mRNA expression in resistant cell lines and normal tissues.
  • Screening of diverse cancer cell lines for TRAG-3 expression.

Main Results:

  • A novel gene, TRAG-3 (Taxol Resistance Associated Gene-3), was identified.
  • TRAG-3 mRNA was significantly overexpressed in taxol-resistant SKOV-3TR cells compared to parental SKOV-3 cells.
  • TRAG-3 exhibits no homology to known cDNAs or proteins.
  • TRAG-3 overexpression was also observed in other drug-resistant cancer cell lines (breast, multiple myeloma).
  • TRAG-3 mRNA expression was minimal in normal tissues but present in various cancer cell lines.

Conclusions:

  • TRAG-3 is a novel gene associated with taxol resistance.
  • TRAG-3 expression is linked to both chemotherapy resistance and the neoplastic phenotype.
  • The findings suggest TRAG-3 as a potential biomarker for chemoresistance and a target for cancer therapy.

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