Differential expression of a human kallikrein 5 (KLK5) splice variant in ovarian and prostate cancer.
The presence of more than one mRNA form is common among kallikrein genes. We identified an mRNA transcript of the human kallikrein gene 5 (KLK5), denoted KLK5 splice variant 1 (KLK5-SV1). This variant has a different 5'-splice site, but encodes the same protein as the classical KLK5 transcript. RT-PCR analysis of this variant transcript expression in 29 human tissues indicated highest expression in the cervix, salivary gland, kidney, mammary gland, and skin. Comparative analysis of the expression levels of KLK5-SV1, another splice variant named KLK5 splice variant 2 (KLK5-SV2), and the classical KLK5 form showed that out of all three mRNA transcripts, the classical form is predominantly expressed (found in more tissues and at higher expression levels) followed by KLK5-SV1. KLK5-SV1 is expressed at high levels in ovarian, pancreatic, breast and prostate cancer cell lines. KLK5-SV1 was also found to be expressed in 9/10 ovarian cancer tissues, but it was not found in one normal ovarian tissue tested. Hormonal regulation experiments suggest that KLK5-SV1 is regulated by steroid hormones in the BT-474 breast cancer cell line. Furthermore, this variant had significantly higher expression in normal prostate tissues compared to their matched cancer tissue counterparts. KLK5-SV1 may have clinical utility in various malignancies and should be further explored as a potential new biomarker for prostate and ovarian cancer.
Kurlender
Lisa
L
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Yousef
George M
GM
Memari
Nader
N
Robb
John-Desmond
JD
Michael
Iacovos P
IP
Borgoño
Carla
C
Katsaros
Dionyssios
D
Stephan
Carsten
C
Jung
Klaus
K
Diamandis
Eleftherios P
EP
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis*; D008297:Male; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D022821:RNA Splice Sites; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D022821:RNA Splice Sites; C400147:KLK5 protein, human; D007610:Kallikreins