Recent evidence suggests that many members of the human kallikrein (KLK) gene 
family are differentially regulated in ovarian cancer and have potential as 
diagnostic and/or prognostic markers. We used the serial analysis of gene 
expression and expressed sequence tag databases of the Cancer Genome Anatomy 
Project to perform in silico analyses of the expression pattern of the 15 human 
KLK genes in normal and cancerous ovarian tissues and cell lines. We found that 
seven KLK genes (KLK5, KLK6, KLK7, KLK8, KLK10, KLK11, and KLK14) are 
up-regulated in ovarian cancer. Probing 2 normal and 10 ovarian cancer serial 
analysis of gene expression libraries with gene-specific tags for each KLK 
indicated that whereas no expression was detected in any normal libraries (with 
the exception of KLK10 and KLK11), these KLKs were found to be expressed with 
moderate densities (103-408 tags per million) in 40-60% of the ovarian cancer 
libraries analyzed. These data were verified by screening the expressed sequence 
tag databases, where 78 of 79 mRNA clones isolated for these genes were from 
ovarian cancer libraries. X-profiler comparison of the pools of normal and 
cancerous ovaries identified a significant difference in expression levels for 
six of the seven KLKs. We experimentally verified the overexpression of six KLK 
proteins in cancer versus normal or benign tissues with highly sensitive and 
specific immunofluorometric assays. A statistically significant stepwise 
increase in protein levels was found among normal, benign, and cancerous ovarian 
tissues. The expression of five KLKs showed a strong degree of correlation at 
the protein level, suggesting the existence of a common mechanism or pathway 
that controls the expression of this group of adjacent genes during ovarian 
cancer progression.