Alternative to the soft-agar assay that permits high-throughput drug and genetic screens for cellular transformation.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

Colony formation in soft agar is the gold-standard assay for cellular transformation in vitro, but it is unsuited for high-throughput screening. Here, we describe an assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the soft-agar assay. Using GILA, we describe high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. Such molecules are unlikely to be found through conventional drug screening, and they include kinase inhibitors and drugs for noncancer diseases. In addition to known oncogenes, the genetic screen identifies genes that contribute to cellular transformation. Lastly, we demonstrate the ability of Food and Drug Administration-approved noncancer drugs to selectively kill ovarian cancer cells derived from patients with chemotherapy-resistant disease, suggesting this approach may provide useful information for personalized cancer treatment.

Year of Publication
2015
Journal
Proc Natl Acad Sci U S A
Volume
112
Issue
18
Pages
5708-13
Date Published
2015 May 05
ISSN
1091-6490
URL
DOI
10.1073/pnas.1505979112
PubMed ID
25902495
PubMed Central ID
PMC4426412
Links
Grant list
R01 CA107486 / CA / NCI NIH HHS / United States
CA 107486 / CA / NCI NIH HHS / United States