Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product

Y. Asano, M. A. Brach, A. Ahlers, S. De Vos, J. H. Butterfield, L. K. Ashman, P. Valent, H. J. Gruss, F. Herrmann

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently indentified stem cell factor, was studied or 12-O- tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10-9 M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN γ, vitamin D3, rednoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.

Original languageEnglish (US)
Pages (from-to)2345-2354
Number of pages10
JournalJournal of Immunology
Volume151
Issue number5
StatePublished - 1993

Fingerprint

Proto-Oncogenes
Oncogene Proteins
Phorbol Esters
Tetradecanoylphorbol Acetate
Down-Regulation
RNA
Proto-Oncogene Proteins c-kit
Camptothecin
Leukemia, Erythroblastic, Acute
Stem Cell Factor
Butyric Acid
Cholecalciferol
Cytarabine
Southern Blotting
Acute Myeloid Leukemia
Mast Cells
Bone Marrow Cells
Northern Blotting
Reverse Transcription
Cell Differentiation

ASJC Scopus subject areas

  • Immunology

Cite this

Asano, Y., Brach, M. A., Ahlers, A., De Vos, S., Butterfield, J. H., Ashman, L. K., ... Herrmann, F. (1993). Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product. Journal of Immunology, 151(5), 2345-2354.

Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product. / Asano, Y.; Brach, M. A.; Ahlers, A.; De Vos, S.; Butterfield, J. H.; Ashman, L. K.; Valent, P.; Gruss, H. J.; Herrmann, F.

In: Journal of Immunology, Vol. 151, No. 5, 1993, p. 2345-2354.

Research output: Contribution to journalArticle

Asano, Y, Brach, MA, Ahlers, A, De Vos, S, Butterfield, JH, Ashman, LK, Valent, P, Gruss, HJ & Herrmann, F 1993, 'Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product', Journal of Immunology, vol. 151, no. 5, pp. 2345-2354.
Asano Y, Brach MA, Ahlers A, De Vos S, Butterfield JH, Ashman LK et al. Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product. Journal of Immunology. 1993;151(5):2345-2354.
Asano, Y. ; Brach, M. A. ; Ahlers, A. ; De Vos, S. ; Butterfield, J. H. ; Ashman, L. K. ; Valent, P. ; Gruss, H. J. ; Herrmann, F. / Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product. In: Journal of Immunology. 1993 ; Vol. 151, No. 5. pp. 2345-2354.
@article{fb7b5cc83dbc4c3d940c47aba9ae3354,
title = "Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product",
abstract = "Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently indentified stem cell factor, was studied or 12-O- tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10-9 M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN γ, vitamin D3, rednoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.",
author = "Y. Asano and Brach, {M. A.} and A. Ahlers and {De Vos}, S. and Butterfield, {J. H.} and Ashman, {L. K.} and P. Valent and Gruss, {H. J.} and F. Herrmann",
year = "1993",
language = "English (US)",
volume = "151",
pages = "2345--2354",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product

AU - Asano, Y.

AU - Brach, M. A.

AU - Ahlers, A.

AU - De Vos, S.

AU - Butterfield, J. H.

AU - Ashman, L. K.

AU - Valent, P.

AU - Gruss, H. J.

AU - Herrmann, F.

PY - 1993

Y1 - 1993

N2 - Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently indentified stem cell factor, was studied or 12-O- tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10-9 M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN γ, vitamin D3, rednoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.

AB - Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently indentified stem cell factor, was studied or 12-O- tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10-9 M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN γ, vitamin D3, rednoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.

UR - http://www.scopus.com/inward/record.url?scp=0027302853&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027302853&partnerID=8YFLogxK

M3 - Article

VL - 151

SP - 2345

EP - 2354

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -