# RELATION OF VM-26 RESISTANCE TO MULTIDRUG RESISTANCE

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 1987 · $94,098

## Abstract

The long-term objective is to define the molecular relationship between
acquired resistance to teniposide (VM-26) and pleiotropic drug resistance
(PDR).  The association of two chromosomes with homogeneously staining
regions (HSRs) in VM-26-resistant L1210 sublines (L1210/VM-26) and of
cross-resistance to etoposide (VP-16), vincristine dactinomycin (DACT), and
adriamycin (ADRIA) provides a model for studying the relationship at the
gene level between acquired resistance to VM-26 and PDR.  The objective
will be accomplished with the techniques of molecular cloning.  The
approach will be:  (1) to demonstrate the presence of similar amplified
gene sequences in the genoic DNA and the HSRs; (2) to compare levels in
L1210 cells and L1210/VM-26 cells of the mRNA transcribed from the gene
that conveys resistance to VM-26; (3) to translate the mRNA for resistance
and compare the product with two novel proteins in L1210/VM-26 cells; (4)
to correlate the copy-number of the amplified gene with resistance to
VM-26; and (5) to examine the similarities of PDR as expressed with
acquired resistance to VCR, DACT, or VM-26 by mouse cells and human cells.
These studies are expected to show that a unique amplified gene, possibly
two, in the genomic DNA and the HSRs relates to VM-26 resistance and that
larger amounts of mRNA for the gene are present in L1210/VM-26 cells than
in L1210 cells.  If the product of this mRNA and either of the 2 novel
proteins in L1210/VM-26 cells is similar, then a phenotypic expression will
have been related to VM-26 resistance and, hopefully, to PDR.  Studies with
these drug-resistant cell lines will indicate the source of the variation
expressed in PDR, that is acquired with resistance to different drugs, as
well as the nature of differences between species.  Drug resistance, which
in reference to patients is more correctly named drug refractoriness,
limits chemotherapy in more than 50% of the cases.  In many instances, the
cancers of patients become resistant to the same drugs that elicit PDR in
laboratory models.  The proposed investigation is expected to relate PDR
with gene amplification, and more importantly to provide the necessary
preparation for future studies in which PDR can be definitively
demonstrated to limit chemotherapy clinically.

## Key facts

- **NIH application ID:** 3178377
- **Project number:** 5R01CA039426-03
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **SAM.gov UEI:** JL4JHE9SDRR3
- **Principal Investigator:** DE WAYNE ROBERTS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $94,098
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178377

## Citation

> US National Institutes of Health, RePORTER application 3178377, RELATION OF VM-26 RESISTANCE TO MULTIDRUG RESISTANCE (5R01CA039426-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178377. Licensed CC0.

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