Abstract
In a genome-wide screen of 684 cancer cell lines, we identified homozygous intragenic microdeletions involving genes encoding components of the apical-basal cell polarity complexes. Among these, PARD3 is disrupted in cell lines and primary tumors from squamous carcinomas and glioblastomas. Reconstituting PARD3 expression in both cell types restores tight junctions and retards contact-dependent proliferation. Searching specifically for small intragenic microdeletions using high-resolution genomic arrays may be complementary to other genomic deletion screens and resequencing efforts in identifying new tumor suppressor genes.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Carcinoma, Squamous Cell / genetics
-
Carcinoma, Squamous Cell / metabolism
-
Carcinoma, Squamous Cell / pathology
-
Cell Cycle Proteins / biosynthesis
-
Cell Cycle Proteins / genetics
-
Cell Line, Tumor
-
Gene Deletion*
-
Genome, Human
-
Glioblastoma / genetics
-
Glioblastoma / metabolism
-
Glioblastoma / pathology
-
Head and Neck Neoplasms / genetics
-
Head and Neck Neoplasms / metabolism
-
Head and Neck Neoplasms / pathology
-
Humans
-
In Situ Hybridization, Fluorescence
-
Membrane Proteins / biosynthesis
-
Membrane Proteins / genetics
-
Neoplasms / genetics*
-
Neoplasms / metabolism
-
Neoplasms / pathology
-
RNA, Messenger / genetics
-
Reverse Transcriptase Polymerase Chain Reaction
-
Tight Junctions / genetics
-
Tight Junctions / metabolism
-
Tight Junctions / pathology
Substances
-
Adaptor Proteins, Signal Transducing
-
Cell Cycle Proteins
-
Membrane Proteins
-
PARD3 protein, human
-
RNA, Messenger