Bw. Park et al., Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases, P NAS US, 96(11), 1999, pp. 6434-6438
Citations number
40
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Conversion of a malignant phenotype into a more normal one can be accomplis
hed either by downregulation of erbB family surface receptors or by creatin
g inactive erbB heterodimers on the cell surface. In this report, we report
the identification and cloning of differentially expressed genes from anti
body-treated vs. untreated fibroblasts transformed by oncogenic p185(neu).
We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northe
rn analysis, was expressed at higher levels in anti-p185(neu)-treated tumor
cells but not in cells expressing internalization defective p185(neu) rece
ptors. This cDNA fragment was identical in amino acid sequence to the recen
tly 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 el
evated on inhibition of the oncogenic phenotype of transformed cells expres
sing erbB family receptors. TBP1 overexpression diminished cell proliferati
on, reduced the ability of the parental cells to form colonies in vitro, an
d almost completely inhibited transforming efficiency in athymic mice when
stably expressed in human tumor cells containing erbB family receptors. Col
lectively, these results suggest that the attenuation of erbB receptor sign
aling seems to be associated with activation/induction or recovery of a fun
ctional tumor suppressor-like gene, TBP1. Disabling erbB tyrosine kinases b
y antibodies or by trans-inhibition represents an initial step in triggerin
g a TBP1 pathway.