# STEROID RESISTANCE IN HUMAN LEUKEMIC CELLS

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 1988 · $129,584

## Abstract

During the last year we have continued to employ both biochemical and
genetic approaches to the study of the acquisition of steroid resistance in
human leukemic cells.  In particular we have concentrated on the analysis
of the normal glucocorticoid receptors of the human lymphoid cell line IM-9
in order to provide a basis for the ultimate analysis of glucocorticoid
receptor mutants in the clonal glucocorticoid-resistant human leukemic cell
lines we have previously isolated.  Using high-resolution 2-dimensional gel
electrophoresis of affinity labeled, immunopurified IM-9 receptors we have
identified two isoforms of the 92 kilodalton human glucocorticoid
receptor.  Analysis of tryptic and chymotryptic digests of these isoforms
has demonstrated that the charge heterogeneity resides in the 24 kilodalton
tryptic fragment of the receptor which contains the steroid binding site.
In addition, we have determined:  (1) that there is no covalent charge
modification of the 92 kilodalton steroid binding protein during activation
of the steroid-receptor complex to its DNA binding form; and (2) that only
the more basic of the two 92 kilodalton isoforms can bind to DNA.  These
results suggest that activation of the steroid-receptor complex does not
involve dephosphorylation of the steroid binding protein.

Our anti-human glucocorticoid receptor antibodies have also been used to
obtain a partial cDNA clone of IM-9 glucocorticoid receptor mRNA.  This
clone was obtained after immunological screening of a lambda gt11 cDNA
expression library.  The availability of this clone will allow direct
analysis of mutant receptor mRNA's and genes as well as provide a powerful
reagent for the study of glucocorticoid receptor gene organization and
regulation.  Thus, we are in an advantageous position to study both the
protein chemistry of mutant glucocorticoid receptors and the mutated genes
which encode them.  (D)

## Key facts

- **NIH application ID:** 3170193
- **Project number:** 2R01CA032226-07
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **SAM.gov UEI:** UYLKBRENAPG5
- **Principal Investigator:** JEFFREY M HARMON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $129,584
- **Award type:** 2
- **Project period:** 1988-08-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170193

## Citation

> US National Institutes of Health, RePORTER application 3170193, STEROID RESISTANCE IN HUMAN LEUKEMIC CELLS (2R01CA032226-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170193. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*