Kallikreins on steroids: structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus.

@article{Lawrence2010KallikreinsOS,
  title={Kallikreins on steroids: structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus.},
  author={Mitchell G. Lawrence and John Lai and Judith A. Clements},
  journal={Endocrine reviews},
  year={2010},
  volume={31 4},
  pages={
          407-46
        }
}
The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and putative proteolytic functions. The kallikrein family is also emerging as a rich source of disease biomarkers with KLK3, commonly known as prostate-specific antigen, being the current serum biomarker for prostate cancer. The kallikrein locus is also notable because it is extraordinarily responsive to steroids and other hormones. Indeed, at least 14 functional hormone… 
View on PubMed
apcbioresource.org.au
208 Citations
Highly Influential Citations
16
Background Citations
102
Methods Citations
3

Figures and Tables from this paper

208 Citations

Citation Type

Citation Type

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance
TLDR
The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide significant benefits for the management of cancer patients.
Selective cleavage of human sex hormone-binding globulin by kallikrein-related peptidases and effects on androgen action in LNCaP prostate cancer cells.
TLDR
It is shown that the cancer-associated serine proteases, kallikrein-related peptidase (KLK)4 and KLK14, bind strongly to sex hormone-binding globulin (SHBG) in glutathione S-transferase interaction analyses and that a stable fragment derived from proteolysis of steroid-bound SHBG retains binding function in vitro.
Evolution of the Plasma and Tissue Kallikreins, and Their Alternative Splicing Isoforms
TLDR
The aim of this study was to address the evolutionary and functional relationships between tissue KLKs and plasma kallikrein, and to examine the evolution of alternative splicing isoforms.
Kallikrein-related peptidases (KLKs) as emerging therapeutic targets: focus on prostate cancer and skin pathologies
TLDR
The central/critical roles of KLK family in several human pathologies highlight KLKs as attractive molecular targets for developing novel therapeutics and novel approaches towards the exploitation of KLks’ therapeutic value are summarized.
Expression profile of human tissue kallikrein 15 provides preliminary insights into its roles in the prostate and testis.
Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact
TLDR
The expression profile of the splice variants of kallikrein-related peptidase 12 in breast cancer patients was analyzed to evaluate their clinical significance and statistical associations with clinicopathological parameters were obtained only from KLK12sv3 variant.
The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6)
TLDR
A comprehensive review will summarise the current findings of KLK6 pathophysiology and discuss its potential as a viable biomarker.
Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases
TLDR
Various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front are discussed to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.
The molecular function of kallikrein‐related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer
TLDR
KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumors and additional work is necessary to determine the benefits and implications of targeting/cotargeting KLK14.
The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness
TLDR
Using in vitro studies, it is demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 523 REFERENCES
Evidence for the novel expression of human kallikrein-related peptidase 3, prostate-specific antigen, in the brain.
TLDR
These findings support the expression of hK3 in neuronal cells reinforcing the concept of h kallikrein-related peptidase 3 as a ubiquitous protein with more multifarious biological activity than previously believed.
The Tissue Kallikrein Family of Serine Proteases: Functional Roles in Human Disease and Potential as Clinical Biomarkers
TLDR
In vitro biochemical studies show that some kallikreins can auto-activate and others can activate each other, suggesting that the kallkreins may participate in an enzymatic cascade similar to that of the coagulation cascade.
Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues*
TLDR
Preliminary results show that KLK-L4 is down-regulated, at the mRNA level, in breast cancer tissues and breast cancer cell lines, and may find applicability as a novel cancer biomarker.
Molecular Cloning of the Human Kallikrein 15 Gene (KLK15)
TLDR
The preliminary results indicate that the expression ofKLK15 is up-regulated by steroid hormones in the LNCaP prostate cancer cell line and the KLK15 gene is also up- regulated, at the mRNA level, in prostate cancer in comparison to normal prostatic tissue.
KLK12 is a novel serine protease and a new member of the human kallikrein gene family-differential expression in breast cancer.
TLDR
Preliminary results indicate that the expression of KLK12 is down-regulated at the mRNA level in breast cancer tissues and is up-regulated by steroid hormones in breast and prostate cancer cell lines.
Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell lines and functional characterization of the KLK10 gene promoter.
Direct Progesterone Receptor and Indirect Androgen Receptor Interactions with the Kallikrein-Related Peptidase 4 Gene Promoter in Breast and Prostate Cancer
TLDR
This is the first study to show that progesterone-regulated KLK4 expression in T47D cells is mediated partly by a hormone response element (K4.pPRE), and the mechanisms mediating the hormonal regulation of KLK 4 in breast and prostate cancer cells are investigated.
The new human tissue kallikrein gene family: structure, function, and association to disease.
TLDR
The recently accumulated knowledge on the human tissue kallikrein gene family is summarized, including gene and protein structure, predicted enzymatic activities, tissue expression, hormonal regulation, and alternative splicing.
KLK 12 Is a Novel Serine Protease and a New Member of the Human Kallikrein Gene Family — Differential Expression in Breast Cancer
TLDR
The preliminary results indicate that the expression of KLK12 is downregulated at the mRNA level in breast cancer tissues and is up-regulated by steroid hormones in breast and prostate cancer cell lines.
Regulation of human tissue kallikrein-related peptidase expression by steroid hormones in 32 cell lines
Abstract Human tissue kallikrein-related peptidases (KLK), which are secreted serine proteases, are encoded by 15 genes located on chromosome 19q13.4. Previous studies have shown that KLK expression…
...
1
2
3
4
5
...