Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases

Byeong Woo Park, Donald M. O'Rourke, Qiang Wang, James G. Davis, Andrew Post, Xiaolan Qian, Mark I. Greene

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Conversion of a malignant phenotype into a more normal one can be accomplished either by downregulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185(neu). We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northern analysis, was expressed at higher levels in anti-p185(neu)- treated tumor cells but not in cells expressing internalization defective p185(neu) receptors. This cDNA fragment was identical in amino acid sequence to the recently cloned mouse Tat binding protein-1 (mTBP1), which has 98.4% homology to the HIV tat-binding protein-1 (TBP1). TBP1 mRNA levels were found to be elevated on inhibition of the oncogenic phenotype of transformed cells expressing erbB family receptors. TBP1 overexpression diminished cell proliferation, reduced the ability of the parental cells to form colonies in vitro, and almost completely inhibited transforming efficiency in athymic mice when stably expressed in human tumor cells containing erbB family receptors. Collectively, these results suggest that the attenuation of erbB receptor signaling seems to be associated with activation/induction or recovery of a functional tumor suppressor-like gene, TBP1. Disabling erbB tyrosine kinases by antibodies or by trans-inhibition represents an initial step in triggering a TBP1 pathway.

Original languageEnglish
Pages (from-to)6434-6438
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number11
DOIs
Publication statusPublished - 1999 May 25

Fingerprint

tat Gene Products
Protein-Tyrosine Kinases
Carrier Proteins
Genes
Human Immunodeficiency Virus tat Gene Products
Complementary DNA
ErbB-2 Receptor
Phenotype
Antibodies
Tumor Suppressor Genes
Nude Mice
ErbB Receptors
Organism Cloning
Amino Acid Sequence
Neoplasms
Down-Regulation
Fibroblasts
Cell Proliferation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Park, Byeong Woo ; O'Rourke, Donald M. ; Wang, Qiang ; Davis, James G. ; Post, Andrew ; Qian, Xiaolan ; Greene, Mark I. / Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 11. pp. 6434-6438.
@article{f1fc2b49206448fd8811bcb979c72fdf,
title = "Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases",
abstract = "Conversion of a malignant phenotype into a more normal one can be accomplished either by downregulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185(neu). We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northern analysis, was expressed at higher levels in anti-p185(neu)- treated tumor cells but not in cells expressing internalization defective p185(neu) receptors. This cDNA fragment was identical in amino acid sequence to the recently cloned mouse Tat binding protein-1 (mTBP1), which has 98.4{\%} homology to the HIV tat-binding protein-1 (TBP1). TBP1 mRNA levels were found to be elevated on inhibition of the oncogenic phenotype of transformed cells expressing erbB family receptors. TBP1 overexpression diminished cell proliferation, reduced the ability of the parental cells to form colonies in vitro, and almost completely inhibited transforming efficiency in athymic mice when stably expressed in human tumor cells containing erbB family receptors. Collectively, these results suggest that the attenuation of erbB receptor signaling seems to be associated with activation/induction or recovery of a functional tumor suppressor-like gene, TBP1. Disabling erbB tyrosine kinases by antibodies or by trans-inhibition represents an initial step in triggering a TBP1 pathway.",
author = "Park, {Byeong Woo} and O'Rourke, {Donald M.} and Qiang Wang and Davis, {James G.} and Andrew Post and Xiaolan Qian and Greene, {Mark I.}",
year = "1999",
month = "5",
day = "25",
doi = "10.1073/pnas.96.11.6434",
language = "English",
volume = "96",
pages = "6434--6438",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "11",

}

Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases. / Park, Byeong Woo; O'Rourke, Donald M.; Wang, Qiang; Davis, James G.; Post, Andrew; Qian, Xiaolan; Greene, Mark I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 11, 25.05.1999, p. 6434-6438.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases

AU - Park, Byeong Woo

AU - O'Rourke, Donald M.

AU - Wang, Qiang

AU - Davis, James G.

AU - Post, Andrew

AU - Qian, Xiaolan

AU - Greene, Mark I.

PY - 1999/5/25

Y1 - 1999/5/25

N2 - Conversion of a malignant phenotype into a more normal one can be accomplished either by downregulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185(neu). We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northern analysis, was expressed at higher levels in anti-p185(neu)- treated tumor cells but not in cells expressing internalization defective p185(neu) receptors. This cDNA fragment was identical in amino acid sequence to the recently cloned mouse Tat binding protein-1 (mTBP1), which has 98.4% homology to the HIV tat-binding protein-1 (TBP1). TBP1 mRNA levels were found to be elevated on inhibition of the oncogenic phenotype of transformed cells expressing erbB family receptors. TBP1 overexpression diminished cell proliferation, reduced the ability of the parental cells to form colonies in vitro, and almost completely inhibited transforming efficiency in athymic mice when stably expressed in human tumor cells containing erbB family receptors. Collectively, these results suggest that the attenuation of erbB receptor signaling seems to be associated with activation/induction or recovery of a functional tumor suppressor-like gene, TBP1. Disabling erbB tyrosine kinases by antibodies or by trans-inhibition represents an initial step in triggering a TBP1 pathway.

AB - Conversion of a malignant phenotype into a more normal one can be accomplished either by downregulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185(neu). We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northern analysis, was expressed at higher levels in anti-p185(neu)- treated tumor cells but not in cells expressing internalization defective p185(neu) receptors. This cDNA fragment was identical in amino acid sequence to the recently cloned mouse Tat binding protein-1 (mTBP1), which has 98.4% homology to the HIV tat-binding protein-1 (TBP1). TBP1 mRNA levels were found to be elevated on inhibition of the oncogenic phenotype of transformed cells expressing erbB family receptors. TBP1 overexpression diminished cell proliferation, reduced the ability of the parental cells to form colonies in vitro, and almost completely inhibited transforming efficiency in athymic mice when stably expressed in human tumor cells containing erbB family receptors. Collectively, these results suggest that the attenuation of erbB receptor signaling seems to be associated with activation/induction or recovery of a functional tumor suppressor-like gene, TBP1. Disabling erbB tyrosine kinases by antibodies or by trans-inhibition represents an initial step in triggering a TBP1 pathway.

UR - http://www.scopus.com/inward/record.url?scp=0033065326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033065326&partnerID=8YFLogxK

U2 - 10.1073/pnas.96.11.6434

DO - 10.1073/pnas.96.11.6434

M3 - Article

C2 - 10339605

AN - SCOPUS:0033065326

VL - 96

SP - 6434

EP - 6438

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 11

ER -