Mechanisms of glucocorticoid resistance in human leukemic cells

Implication of abnormal 90 and 70 kDa heat shock proteins

S. Kojika, K. Sugita, T. Inukai, M. Saito, K. Iijima, T. Tezuka, K. Goi, K. Shiraishi, Takehiko Mori, T. Okazaki, K. Kagami, K. Ohyama, S. Nakazawa

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The unliganded glucocorticoid receptor is a multi-oligomer complex consisting of a ligand-binding protein with which two 90 kDa heat shock proteins (hsp90s) are associated. Upon binding of glucocorticoid to the receptor, the ligand binding protein, which dissociated from hsp90s, enters the nucleus, binds to a specific site in DNA, and thus transmits signal(s). The 70 kDa heat shock protein (hsp70) also works as a molecular chaperone when the ligand-binding protein enters the nucleus. Regarding the mechanisms of glucocorticoid resistance, a decreased expression of glucocorticoid receptor and a mutant protein with low ligand binding affinity have been reported. In the present study, to address other mechanisms of glucocorticoid resistance, we examined the expression of hsp90 and hsp70 in addition to the number of glucocorticoid-binding sites and their affinity using glucocorticoid-sensitive and -resistant human leukemic cell lines. We showed that two of nine resistant cell lines with normal glucocorticoid-binding proteins express aberrant hsp90 and extremely low hsp70, while another seven resistant cell lines had decreased binding sites with normal hsps. These results suggest that there are at least two independent mechanisms of glucocorticoid resistance in human leukemic cell lines: the decreased ligand binding sites and the abnormal hsps expression.

Original languageEnglish
Pages (from-to)994-999
Number of pages6
JournalLeukemia
Volume10
Issue number6
Publication statusPublished - 1996 Jun
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Ligands
Glucocorticoid Receptors
Carrier Proteins
Glucocorticoids
Cell Line
Binding Sites
HSP90 Heat-Shock Proteins
Molecular Chaperones
Mutant Proteins
Glucocorticoid Receptor Deficiency
DNA

Keywords

  • Glucocorticoid receptor
  • Glucocorticoid resistance
  • hsp70
  • hsp90
  • Leukemia

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Kojika, S., Sugita, K., Inukai, T., Saito, M., Iijima, K., Tezuka, T., ... Nakazawa, S. (1996). Mechanisms of glucocorticoid resistance in human leukemic cells: Implication of abnormal 90 and 70 kDa heat shock proteins. Leukemia, 10(6), 994-999.

Mechanisms of glucocorticoid resistance in human leukemic cells : Implication of abnormal 90 and 70 kDa heat shock proteins. / Kojika, S.; Sugita, K.; Inukai, T.; Saito, M.; Iijima, K.; Tezuka, T.; Goi, K.; Shiraishi, K.; Mori, Takehiko; Okazaki, T.; Kagami, K.; Ohyama, K.; Nakazawa, S.

In: Leukemia, Vol. 10, No. 6, 06.1996, p. 994-999.

Research output: Contribution to journalArticle

Kojika, S, Sugita, K, Inukai, T, Saito, M, Iijima, K, Tezuka, T, Goi, K, Shiraishi, K, Mori, T, Okazaki, T, Kagami, K, Ohyama, K & Nakazawa, S 1996, 'Mechanisms of glucocorticoid resistance in human leukemic cells: Implication of abnormal 90 and 70 kDa heat shock proteins', Leukemia, vol. 10, no. 6, pp. 994-999.
Kojika S, Sugita K, Inukai T, Saito M, Iijima K, Tezuka T et al. Mechanisms of glucocorticoid resistance in human leukemic cells: Implication of abnormal 90 and 70 kDa heat shock proteins. Leukemia. 1996 Jun;10(6):994-999.
Kojika, S. ; Sugita, K. ; Inukai, T. ; Saito, M. ; Iijima, K. ; Tezuka, T. ; Goi, K. ; Shiraishi, K. ; Mori, Takehiko ; Okazaki, T. ; Kagami, K. ; Ohyama, K. ; Nakazawa, S. / Mechanisms of glucocorticoid resistance in human leukemic cells : Implication of abnormal 90 and 70 kDa heat shock proteins. In: Leukemia. 1996 ; Vol. 10, No. 6. pp. 994-999.
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