# MECHANISMS REGULATING CELL RESISTANCE TO ADRIAMYCIN

> **NIH NIH R01** · KANSAS STATE UNIVERSITY · 1987 · $79,008

## Abstract

Evidence has been obtained that adriamycin resistance in Chinese hamster
lung cells is regulated by phosphorylation of a plasma membrane
glycoprotein (P-180).  We have found that agents which enhance drug uptake
in resistant cells induce a parallel superphosphorylation of P-180.
Several lines of evidence indicates that as P-180 is superphosphorylated
the protein becomes biologically inactive and this results in the
conversion of the resistant cell to a drug sensitive phenotype.
Understanding the details of this reaction should provide considerable
insight into the basis of adriamycin resistance.  In the present study we
will analyze in detail the molecular events involved in the regulation of
P-180 phosphorylation.  Detailed studies will be carried out to analyze the
sites of phosphorylation of P-180 and the mechanism by which these sites
are modulated during the superphosphorylation reaction.  We will also
determine if during superphosphorylation there is a topological
rearrangement of P-180 in the plasma membrane.  Additional studies will be
carried out to identify and characterize the protein kinase(s) activity
involved in the phosphorylation of P-180.  Factors which may regulate the
activity of these enzymes will also be examined.

Studies will also be conducted to determine if the superphosphorylation of
P-180 could serve as a sensitive assay for detecting a small number of
resistant cells in a heterogeneous population of resistant and sensitive
cells.

Mechanisms regulating adriamycin resistance in human tumor cells will be
studied in detail.

## Key facts

- **NIH application ID:** 3175359
- **Project number:** 2R01CA037585-04
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **SAM.gov UEI:** CFMMM5JM7HJ9
- **Principal Investigator:** MELVIN S CENTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $79,008
- **Award type:** 2
- **Project period:** 1984-07-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175359

## Citation

> US National Institutes of Health, RePORTER application 3175359, MECHANISMS REGULATING CELL RESISTANCE TO ADRIAMYCIN (2R01CA037585-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175359. Licensed CC0.

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