Several prognostic studies have shown that the combination of KLK6
with CA-125 enhances their diagnostic power (4,5).
These genes include angiogenic/vascular cell growth factors (VEGF, PLGF, ADM, ANGPT2, TGFB2), vasoactive serine proteases (KLK2, KLK6
, KLK9, KLK22), and vascular endothelial receptors (IL17R, BDKRB1, ENG, GNA13).
The amounts of 18S rRNA and mRNAs encoded by KLK5, KLK6
, KLK7, KLK10,
Recent work has demonstrated roles for KLK5 and 7 in skin desquamation (7), and for KLK6
in the brain (8).
30) found no overexpression of the 15 tissue kallikreins in breast cancer tissue compared with healthy breast tissue and down-regulation of the expression of at least 4 tissue kallikrein genes (KLK5, KLK6
, KLK8, and KLK10) in breast cancer tissue.
For example, we found that KLK6
and KLK13 have a splice variant with 3'-coding exon 3 extension by ~100 by (close to the length of the retained intron III in the genes examined here).
gene encodes for a trypsin-like serine protease 244 amino acids in length, of which 16 amino acids constitute the signal peptide and 5 amino acids (Glu-Glu-Gln-Asn-Lys) constitute the activation peptide.
Previously, several other kallikreins, including KLK4, KLK5, KLK6
, KLK7, KLK8, KLK9, KLK10, KLK11, KLK14, and KLK15, have been associated with various forms of malignancy and especially cancers of the ovary, breast, prostate, and testis [reviewed in Refs.
(zyme/protease M) was isolated by differential display from an ovarian cancer library (57), and KLK10 (NES1) was cloned by subtractive hybridization from a breast cancer library (58) and later shown to act as a tumor suppressor gene (59).
On the basis of the amino acid sequences, the closest relatives of KLK4 within the human kallikrein gene family are those that encode PSA (38% identity), the human stratum corneum chymotryptic enzyme (45% identity), and KLK6
(zyme/ neurosin/protease M; 38% identity) (6); the last and KLK10 are implicated in ovarian cancer (7, 8).
(zyme/protease M/neurosin) is expressed in primary breast and ovarian cancers (16), and preliminary studies indicate that it may have utility as a serum biomarker for ovarian carcinoma (17).
New gene Previous gene New protein symbol (a,b) symbol(s) symbol KLK1 KLK1 hK1 KLK3 KLK3 hK3 KLK2 KLK2 hK2 KLK4 PRSS17, KLK-L1, KLK4 hK4 KLK5 KLK-L2 hK5 KLK6
PRSS9 hK6 KLK7 PRSS6 hK7 KLKS PRSS19 hK8 KLK9 KLK-L3 hK9 KLK10 PRSSL1, hK10 KLK11 PRSS20 hK11 KLK12 KLK-L5 hK12 KLK13 KLK-L4 hK13 KLK14 KLK-L6 hK14 New gene symbol (a,b) Other protein names/symbols KLK1 Pancreatic/renal kallikrein, hPRK KLK3 Prostate-specific antigen, PSA KLK2 Human glandular kallikrein 1, hGK-1 KLK4 Prostase, KLK-L1 protein, EMSP1 KLK5 KLK-L2 protein, HSCTE KLK6
Zyme, protease M, neurosin KLK7 HSCCE KLKS Neuropsin, ovasin, TADG-14 KLK9 KLK-L3 protein KLK10 NES1 protein KLK11 TLSP/hippostasin KLK12 KLK-L5 protein KLK13 KLK-L4 protein KLK14 KLK-L6 protein New gene GenBank symbol (a,b) Accession No.