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KLK14  -  kallikrein-related peptidase 14

Homo sapiens

Synonyms: KLK-L6, KLKL6, Kallikrein-14, Kallikrein-like protein 6, hK14
 
 
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Disease relevance of KLK14

  • Given the above, we determined the prognostic significance of KLK14 expression in breast cancer [1].
  • Similar to other kallikrein genes, KLK14 was found to be regulated by steroid hormones, particularly androgens and progestins, in breast and ovarian cancer cell lines [1].
  • We studied KLK14 expression in 178 histologically confirmed epithelial breast carcinomas by quantitative reverse transcription-polymerase chain reaction and correlated with clinicopathological variables (tumour stage, grade, histotype etc.) and with outcome (disease-free survival and overall survival), monitored over a median of 76 months [1].
  • Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts [2].
 

High impact information on KLK14

  • Given that KLK14 is hormonally regulated, differentially expressed in endocrine-related cancers, and a prognostic marker for breast and ovarian cancer at the mRNA level, we hypothesize that its encoded protein, hK14, like hK3/prostate-specific antigen, may constitute a new biomarker for endocrine-related malignancies [3].
  • Human kallikrein 14: a new potential biomarker for ovarian and breast cancer [3].
  • Our preliminary results show that KLK14 is down-regulated, at the mRNA level, in breast, testicular, prostatic, and ovarian cancer [4].
  • KLK14 is expressed in a variety of tissues, but the highest levels of KLK14 are found in the central nervous system, including brain, cerebellum, and spinal cord [4].
  • Human tissue kallikrein 14 (KLK14) is a novel extracellular serine protease [5].
 

Chemical compound and disease context of KLK14

 

Biological context of KLK14

 

Anatomical context of KLK14

  • KLK14 could be immunohistochemically detected in sweat ducts, preferentially in the intraepidermal parts (the acrosyringium), and in sweat glands [10].
  • In situ hybridization revealed that, in prostate, KLK14 is expressed by both benign and malignant glandular epithelial cells, thus exhibiting an expression pattern similar to that of two other prostatic kallikreins, KLK2 and KLK3, which encode K2 and prostate-specific antigen, respectively [7].
  • KLK14 is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues [2].
  • KLK14 expression was localized in the uterine L and G epithelium, and stroma throughout the endometrium after day 10 [9].
 

Associations of KLK14 with chemical compounds

  • KLK14 also has independent prognostic value in subgroups of patients with a tumour size </=2 cm and positive nodal, oestrogen receptor and progestin receptor status [1].
 

Other interactions of KLK14

  • This was in spite of very low levels of KLK14 protein compared to KLK5 and KLK7 [10].
 

Analytical, diagnostic and therapeutic context of KLK14

  • KLK14 overexpression was found to be a significant predictor of decreased disease-free survival (hazard ratio of 2.31, P=0.001) and overall survival (hazard ratio of 2.21, P=0.005) [1].
  • KLK14 could be detected by immunoblotting in normal superficial stratum corneum of all individuals examined [10].
  • By using our novel immunoassay, the normal and/or diseased skin, breast, prostate, and ovary contained the highest concentration of KLK14 [5].
  • KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P = 0.027), an issue that had not been clarified recently [6].
  • We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable [6].

References

  1. Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis. Yousef, G.M., Borgoño, C.A., Scorilas, A., Ponzone, R., Biglia, N., Iskander, L., Polymeris, M.E., Roagna, R., Sismondi, P., Diamandis, E.P. Br. J. Cancer (2002) [Pubmed]
  2. Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues. Yousef, G.M., Stephan, C., Scorilas, A., Ellatif, M.A., Jung, K., Kristiansen, G., Jung, M., Polymeris, M.E., Diamandis, E.P. Prostate (2003) [Pubmed]
  3. Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Borgoño, C.A., Grass, L., Soosaipillai, A., Yousef, G.M., Petraki, C.D., Howarth, D.H., Fracchioli, S., Katsaros, D., Diamandis, E.P. Cancer Res. (2003) [Pubmed]
  4. Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies. Yousef, G.M., Magklara, A., Chang, A., Jung, K., Katsaros, D., Diamandis, E.P. Cancer Res. (2001) [Pubmed]
  5. Expression and Functional Characterization of the Cancer-related Serine Protease, Human Tissue Kallikrein 14. Borgoño, C.A., Michael, I.P., Shaw, J.L., Luo, L.Y., Ghosh, M.C., Soosaipillai, A., Grass, L., Katsaros, D., Diamandis, E.P. J. Biol. Chem. (2007) [Pubmed]
  6. Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status. Fritzsche, F., Gansukh, T., Borgoño, C.A., Burkhardt, M., Pahl, S., Mayordomo, E., Winzer, K.J., Weichert, W., Denkert, C., Jung, K., Stephan, C., Dietel, M., Diamandis, E.P., Dahl, E., Kristiansen, G. Br. J. Cancer (2006) [Pubmed]
  7. Identification and characterization of KLK14, a novel kallikrein serine protease gene located on human chromosome 19q13.4 and expressed in prostate and skeletal muscle. Hooper, J.D., Bui, L.T., Rae, F.K., Harvey, T.J., Myers, S.A., Ashworth, L.K., Clements, J.A. Genomics (2001) [Pubmed]
  8. Steroid hormone regulation and prognostic value of the human kallikrein gene 14 in ovarian cancer. Yousef, G.M., Fracchioli, S., Scorilas, A., Borgoño, C.A., Iskander, L., Puopolo, M., Massobrio, M., Diamandis, E.P., Katsaros, D. Am. J. Clin. Pathol. (2003) [Pubmed]
  9. Porcine endometrial and conceptus tissue kallikrein 1, 4, 11, and 14 gene expression. Fernando, S.C., Buck, J.S., Ashworth, M.D., Ross, J.W., Geisert, R.D., Desilva, U. Reproduction (2006) [Pubmed]
  10. Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum. Stefansson, K., Brattsand, M., Ny, A., Glas, B., Egelrud, T. Biol. Chem. (2006) [Pubmed]
 
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