In the present study, we analyzed human ovarian carcinoma cell lines for 
abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in 
cyclin-dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using 
molecular biology techniques. For the Rb gene, in all six cell lines (PA-1, 
Caov-3 and -4, OVCAR-3, SK-OV-3, and Kuramochi), Rb gene abnormality was not 
detected using Southern blotting. In the Caov-3 cell line transcripts were not 
detectable by either Northern blot or polymerase chain reaction. Sequence 
analysis of the entire coding region of the Rb gene revealed point mutations 
(AAC to GAC) resulting in codon 123 (Asn to Asp) changes in the Caov-4 cell 
line. In the PA-1 cell line both wild-type Rb and mutant-type Rb (codon 798: CGG 
to TGG) were expressed, and in the OVCAR-3 cell line both wild-type Rb and 
mutant-type Rb (codon 704: ATG to GTG) were expressed. In four of six human 
ovarian carcinoma cell lines Rb gene abnormality was detected. For the p16INK4 
and p15INK4B genes, only the SK-OV-3 cell line had abnormalities. There was a 
gene rearrangement or minor deletion of the p16INK4 gene in the SK-OV-3 cell 
line, while the p15INK4B gene was deleted in this cell line. In the SK-OV-3 cell 
line no mRNAs of p16INK4 and p15INK4B were expressed. At the point of Rb gene 
inactivation, we can explain five cell lines of six: four cell lines had 
abnormalities in the Rb gene itself, which is another mechanism by which the Rb 
gene is inactivated, while one cell line (SK-OV-3) had abnormalities in CDK4 
inhibitor genes, another of the inactivation mechanisms of the Rb gene. These 
data suggest that abnormalities of Rb and CDK4 inhibitor genes (p16INK4, 
p15INK4B) may be involved in human ovarian carcinogenesis.