Adenovirus-mediated Gene Transfer of Dominant Negative Ha-Ras Inhibits Proliferation of Primary Meningioma Cells

Adenovirus-mediated Gene Transfer of Dominant Negative Ha-Ras Inhibits Proliferation of Primary... AbstractOBJECTIVE:Previous studies demonstrated that activation of receptor tyrosine kinases in human meningiomas by an autocrine or paracrine growth-stimulatory loop plays an important role in meningioma proliferation. Although it is well established that the proliferative signal from protein tyrosine kinase receptors is transduced through Ras proteins, the relevance of the Ras pathway in meningioma proliferation, to our knowledge, has not been studied. The purpose of this study was, therefore, to determine whether Ras proteins are functionally important in meningioma proliferation.METHODS:Meningioma cells of nine primary cell cultures were infected with the recombinant adenovirus Ad-rasNl7 encoding the dominant negative Ras protein or control adenovirus Ad-pAC. Ras-N17 is a Ras mutant protein with substitution of asparagine for serine at position 17 in the cellular Ha-Ras protein that inhibits function of all endogenous cellular Ras proteins. Proliferation of meningioma cells was measured using [3H]thymidine or 5-bromo-2'-deoxyuridine labeling and detection assays.RESULTS:Infection of meningioma cells with Ad-rasN17 dramatically increased the expression levels of the Ras-N17 mutant protein and inhibited phosphorylation of the mitogen-activated protein kinases, compared with uninfected cells or cells infected with the control adenovirus. Suppression of Ras proteins inhibited proliferation of all exponentially growing and growth-arrested meningioma cells stimulated with serum.CONCLUSION:The obtained results suggest that proliferation of primary meningioma cells is dependent on the Presence of functional Ras proteins. Therefore, inhibition of the Ras pathway may be important in preventing growth factor-stimulated meningioma proliferation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Adenovirus-mediated Gene Transfer of Dominant Negative Ha-Ras Inhibits Proliferation of Primary Meningioma Cells

Adenovirus-mediated Gene Transfer of Dominant Negative Ha-Ras Inhibits Proliferation of Primary Meningioma Cells

EXPERIMENTAL STUDIES Adenovirus-mediated Gene Transfer of Dominant Negative Ha-Ras Inhibits Proliferation of Primary Meningioma Cells Junyan Shu, Ph.D., Joung H. Lee, M .D ., Jyoti A. Harwalkar, M.S., Susan Oh-Siskovic, M.S., Dennis W . Stacey, Ph.D., Mladen Golubic, M .D ., Ph.D. Departm ents of M o le cu la r Biology (JS, SO-S, D W S) and N eurological Surgery (JH L, JA H , M G ), C le ve lan d C lin ic Foundation, C le ve la n d , O h io OBJECTIVE: Previous studies demonstrated that activation of receptor tyrosine kinases in human meningiomas by an autocrine or paracrine growth-stimulatory loop plays an important role in meningioma proliferation. Although it is well established that the proliferative signal from protein tyrosine kinase receptors is transduced through Ras proteins, the relevance of the Ras pathway in meningioma proliferation, to our knowledge, has not been studied. The purpose of this study was, therefore, to determine whether Ras proteins are functionally important in meningioma proliferation. METHODS: Meningioma cells of nine prim ary cell cultures were infected with the recombinant adenovirus Ad-rasNl7 encoding the dom inant negative Ras protein or control adenovirus Ad-pAC. Ras-N17 is a Ras mutant protein with substitution of asparagine for serine at position 17 in the cellular Ha-Ras protein that inhibits function of all endogenous cellular Ras proteins. Proliferation of meningioma cells was measured using [ *H]thy- midine or 5-bromo-2'-deoxyuridine labeling and detection assays. RESULTS: Infection of meningioma cells with Ad-rasN17 dram atically increased the expression levels of the Ras-N17 mutant protein and inhibited phosphorylation of the mitogen-activated protein kinases, compared with unin­ fected cells or cells infected w ith the control adenovirus. Suppression of Ras proteins inhibited proliferation of all exponentially growing and growth-arrested meningioma cells stimulated with serum. CONCLUSION: The obtained results...
Loading next page...
 
/lp/ou_press/adenovirus-mediated-gene-transfer-of-dominant-negative-ha-ras-inhibits-f0DJUt5z7h
Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199903000-00080
Publisher site
See Article on Publisher Site

Abstract

AbstractOBJECTIVE:Previous studies demonstrated that activation of receptor tyrosine kinases in human meningiomas by an autocrine or paracrine growth-stimulatory loop plays an important role in meningioma proliferation. Although it is well established that the proliferative signal from protein tyrosine kinase receptors is transduced through Ras proteins, the relevance of the Ras pathway in meningioma proliferation, to our knowledge, has not been studied. The purpose of this study was, therefore, to determine whether Ras proteins are functionally important in meningioma proliferation.METHODS:Meningioma cells of nine primary cell cultures were infected with the recombinant adenovirus Ad-rasNl7 encoding the dominant negative Ras protein or control adenovirus Ad-pAC. Ras-N17 is a Ras mutant protein with substitution of asparagine for serine at position 17 in the cellular Ha-Ras protein that inhibits function of all endogenous cellular Ras proteins. Proliferation of meningioma cells was measured using [3H]thymidine or 5-bromo-2'-deoxyuridine labeling and detection assays.RESULTS:Infection of meningioma cells with Ad-rasN17 dramatically increased the expression levels of the Ras-N17 mutant protein and inhibited phosphorylation of the mitogen-activated protein kinases, compared with uninfected cells or cells infected with the control adenovirus. Suppression of Ras proteins inhibited proliferation of all exponentially growing and growth-arrested meningioma cells stimulated with serum.CONCLUSION:The obtained results suggest that proliferation of primary meningioma cells is dependent on the Presence of functional Ras proteins. Therefore, inhibition of the Ras pathway may be important in preventing growth factor-stimulated meningioma proliferation.

Journal

NeurosurgeryOxford University Press

Published: Mar 1, 1999

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off