Identification and characterization of KLK-L4, a new kallikrein-like gene that appears to be down-regulated in breast cancer tissues

被引:79
作者
Yousef, GM
Chang, A
Diamandis, EP
机构
[1] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X5, Canada
关键词
D O I
10.1074/jbc.275.16.11891
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Kallikreins are a subgroup of serine proteases and these proteolytic enzymes have diverse physiological functions in many tissues. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. In rodents, kallikreins constitute a large multigene family, but in humans, only three genes were identified. By using the positional candidate gene approach, we were able to identify a new kallikrein-like gene, tentatively named KLK-L4 (for kallikrein-like gene 4), This new gene maps to chromosome 19q13.3-q13.4, is formed of five coding exons and four introns, and shows structural similarity to other kallikreins and kallikrein-like genes. KLK-L4 is expressed in a variety of tissues including prostate, salivary gland, breast, and testis, Our preliminary results show that KLK-L4 is down-regulated, at the mRNA level, in breast cancer tissues and breast cancer cell lines. Its expression is regulated by steroid hormones in the breast cancer cell line BT-474. This gene may be involved in the pathogenesis and/or progression of breast cancer and may find applicability as a novel cancer biomarker.
引用
收藏
页码:11891 / 11898
页数:8
相关论文
共 40 条
[1]   Biochemistry and regulation of pre-mRNA splicing [J].
Adams, MD ;
Rudner, DZ ;
Rio, DC .
CURRENT OPINION IN CELL BIOLOGY, 1996, 8 (03) :331-339
[2]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[3]   A novel protease homolog differentially expressed in breast and ovarian cancer [J].
Anisowicz, A ;
Sotiropoulou, G ;
Stenman, G ;
Mok, SC ;
Sager, R .
MOLECULAR MEDICINE, 1996, 2 (05) :624-636
[4]   TISSUE-SPECIFIC EXPRESSION OF KALLIKREIN-RELATED GENES IN THE RAT [J].
ASHLEY, PL ;
MACDONALD, RJ .
BIOCHEMISTRY, 1985, 24 (17) :4520-4527
[5]   A comparative analysis of prostate-specific antigen gene sequence in benign and malignant prostate tissue [J].
Baffa, R ;
Moreno, JG ;
Monne, M ;
Veronese, ML ;
Gomella, LG .
UROLOGY, 1996, 47 (06) :795-800
[6]  
Black MH, 1999, CLIN CHEM, V45, P790
[7]  
CHEN LM, 1994, BRAZ J MED BIOL RES, V27, P1829
[8]  
CLEMENTS J, 1997, KININ SYSTEM, P71
[9]  
Dayhoff M.O., 1978, ATLAS PROTEIN SEQ ST, V5
[10]   Prostate-specific antigen: Its usefulness in clinical medicine [J].
Diamandis, EP .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 1998, 9 (08) :310-316