Functional evidence for an ovarian cancer tumor suppressor gene on chromosome 22 by microcell-mediated chromosome transfer.
The identity of many tumor suppressor genes important in epithelial ovarian cancer tumorigenesis remains unknown. In an effort to localize a novel tumor suppressor on chromosome 22, a psv2neo tagged human chromosome 22 was transferred into the malignant epithelial ovarian cancer cell line, SKOv-3, by microcell-mediated chromosome transfer. Complete suppression of the transformed phenotype was observed in 16 of 18 individual microcell hybrid clones as evidenced by the complete abrogation of cell growth under anchorage-independent conditions. In vitro doubling times were also dramatically reduced, as was the ability to form subcutaneous tumors in CD1 nu/nu mice. Only one polymorphic marker, D22S429, segregated with decreased transformation and tumorigenic potential, suggesting that an unrecognized tumor suppressor may localize to chromosome 22q11-q12. These data provide functional support for the presence of a novel tumor suppressor locus (or loci) on chromosome 22 that is important in ovarian cancer tumorigenesis.
Kruzelock
R P
RP
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, TX 77030, USA.
Cuevas
B D
BD
Wiener
J R
JR
Xu
F J
FJ
Yu
Y
Y
Cabeza-Arvelaiz
Y
Y
Pershouse
M
M
Lovell
M M
MM
Killary
A M
AM
Mills
G B
GB
Bast
R C
RC
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D002459:Cell Fusion; D002892:Chromosomes, Human, Pair 22; D005260:Female; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008819:Mice, Nude; D018895:Microsatellite Repeats; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D013489:Suppression, Genetic; D014407:Tumor Cells, Cultured
D005819:Genetic Markers