Molecular Cloning of the Human Kallikrein 15 Gene (KLK15)

Abstract

Kallikreins are a subgroup of serine proteases with diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. By using molecular cloning techniques, we identified a new human kallikrein gene, tentatively named KLK15 (for kallikrein 15 gene). This new gene maps to chromosome 19q13.4 and is located between the KLK1 and KLK3 genes. KLK15 is formed of five coding exons and four introns, and shows structural similarity to other kallikreins and kallikrein-like genes. KLK15 has three alternatively spliced forms and is primarily expressed in the thyroid gland and to a lower extent in the prostate, salivary, and adrenal glands and in the colon testis and kidney. Our preliminary results indicate that the expression of KLK15 is up-regulated by steroid hormones in the LNCaP prostate cancer cell line. The KLK15 gene is also up-regulated, at the mRNA level, in prostate cancer in comparison to normal prostatic tissue. KLK15 up-regulation was found to be associated with more aggressive forms of prostate cancer. This newly discovered gene has the potential of being used as a diagnostic and/or prognostic marker for prostate cancer.

TheTMPRSS2 gene encoding transmembrane serine protease is overexpressed in a majority of prostate cancer patients: Detection of mutatedTMPRSS2 form in a case of aggressive disease

“…For example, prostase (KLK4) is suggested to be associated with prostate cancer, 9 and KLK15, one of the most recently discovered kallikrein genes, is upregulated in this disease. 10 KLK-L4 in turn is downregulated in breast cancer. 11 One important task in the future will be to clarify the exact functions of kallikreins and other types of serine proteases during the initiation and progression of cancer.…”

Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis

“…The kallikrein genes, denoted KLK1 -KLK15, are located on chromosome 19q13.4 and encode for corresponding kallikrein enzymes, hK1 -hK15 Yousef et al, 2000b). Accumulating evidence indicates that many members of this family are differentially expressed in certain malignancies, including prostate (Rittenhouse et al, 1998;Magklara et al, 1999;Barry, 2001;Yousef et al, 2001c;Diamandis et al, 2002), testicular (Luo et al, 2001c), breast (Yousef et al, 2000a,c) and ovarian (Anisowicz et al, 1996;Diamandis et al, 2000c;Kim et al, 2001;Luo et al, 2001b;Magklara et al, 2001;Obiezu et al, 2001;Yousef et al, 2001a) cancers. Also, many kallikrein genes examined thus far are under steroid hormone regulation, further suggesting a role for these enzymes in endocrine-related tissues (Yousef and Diamandis, 2002).…”

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer

“…KLK3 is flanked by the KLK2 gene (encoding for human glandular kallikrein protein; hK2), and by the KLK15 (Yousef et al, 2001b). In addition to its wide applicability as the best marker for prostate cancer (Diamandis, 1998), hK3, was recently found to be expressed in other tissues, including the female breast (Black and Diamandis, 2000).…”

“…Prostate specific antigen (PSA) protein in tumour cytosols was found to be an independent marker for favourable prognosis in breast cancer (Yu et al, 1995). KLK15 (encoding for hK15, a protein also named 'prostinogen') is the most recently cloned member of the human kallikrein gene family (Takayama et al, 2001;Yousef et al, 2001b). It is formed of five coding exons and encodes for a serine protease of a predicted molecular weight of about 28 kDa.…”