The Molecular Biology of the Kallikreins and their Roles in Inflammation

Clements, Judith A.

doi:10.1016/b978-012249340-9/50007-3

Cited by 48 publications

(51 citation statements)

References 263 publications

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“…Kallikreins are a subgroup of serine proteases traditionally defined by their ability to release vasoactive peptides (kinins) from kininogens (23). However, it is now recognized that in both humans and rodents, kallikreins exhibit a variety of functions in different tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The large size of the kallikrein gene family in other species, such as rat and mouse, where kallikreins are encoded by [13][14][15][16][17][18][19][20][21][22][23][24] genes (12)(13), and the recent identification of new kallikreinlike genes suggested that the human kallikrein gene family may be larger than previously thought. The rodent kallikrein genes are located in clusters on chromosome 7, and the region between two mouse kallikrein genes in a cluster can be as small as 3-7 kb (14).…”

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confidence: 99%

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Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Yousef¹,

Chang²,

Diamandis³

2000

Journal of Biological Chemistry

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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.Prostate-specific antigen (PSA) 1 testing has revolutionized the management of patients with prostate cancer (1). The PSA gene (KLK3) is a member of the human tissue kallikrein gene family, which is also comprised of human glandular kallikrein 2 (KLK2) (2) and pancreatic/renal kallikrein (KLK1) (3) genes. More recently, new serine proteases with a high degree of homology to the kallikrein genes were cloned (4 -9). The successful diagnostic use of PSA in prostate cancer suggests that other related or unrelated molecules might be discovered and serve as diagnostic tests for breast, ovarian, and other cancers. In addition to PSA, human glandular kallikrein 2 (encoded by the KLK2 gene) may be useful as an adjuvant diagnostic marker for prostate cancer (10). Accumulating evidence indicates that some members of the kallikrein gene family are implicated in carcinogenesis. The normal epithelial cell-specific 1 gene (NES1) was found to be a tumor suppressor (11) that is down-regulated during breast cancer progression. The zyme/ protease M/neurosin gene is expressed in primary breast cancers but is down-regulated at metastatic sites (4).The large size of the kallikrein gene family in other species, such as rat and mouse, where kallikreins are encoded by 13-24 genes (12-13), and the recent identification of new kallikreinlike genes suggested that the human kallikrein gene family may be larger than previously thought. The rodent kallikrein genes are located in clusters on chromosome 7, and the region between two mouse kallikrein genes in a cluster can be as small as 3-7 kb (14).In our efforts to identify new kallikrein-like genes that might be useful as diagnostic and/or prognostic markers for cancer, we studied a genomic area of ϳ300 kb around chromosome 19q13.3-q13.4, where the known human kallikrein genes are localized. We were able to identify three new kallikrein-like genes; KLK-L1 (for kallikrein-like gene 1) (15) KLK-L2 (fo...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Yousef¹,

Chang²,

Diamandis³

2000

Journal of Biological Chemistry

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“…T he basic components of the kallikrein-kinin system were discovered in the 1930s (Kraut et al 1930;Clements 1997). The human tissue kallikrein gene family was identified in the 1980s (reviewed in Diamandis et al 2000b;Yousef and Diamandis 2001).…”

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confidence: 99%

Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

Petraki

Karavana

Luo

et al. 2002

J Histochem Cytochem.

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The normal epithelial cell-specific 1 (NES1) gene (official name kallikrein gene 10, KLK10) was recently cloned and encodes for a putative secreted serine protease (human kallikrein 10, hK10). Several studies have confirmed that hK10 shares many similarities with the other kallikrein members at the DNA, mRNA, and protein levels. The enzyme was found in biological fluids, tissue extracts, and serum. Here we report the first detailed immunohistochemical (IHC) localization of hK10 in normal human tissues. We used the streptavidin-biotin method with two hK10-specific antibodies, a polyclonal rabbit and a monoclonal mouse antibody, developed in house. We analyzed 184 paraffin blocks from archival, current, and autopsy material, prepared from almost every normal human tissue. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. Previously, we reported the expression of another novel human kallikrein, hK6, by using similar techniques. The IHC expression of hK10 was generally cytoplasmic and not organ-specific. A variety of normal human tissues expressed the protein. Glandular epithelia constituted the main immunoexpression sites, with representative organs being the breast, prostate, kidney, epididymis, endometrium, fallopian tubes, gastrointestinal tract, bronchus, salivary glands, bile ducts, and gallbladder. The choroid plexus epithelium, the peripheral nerves, and some neuroendocrine organs (including the islets of Langerhans, cells of the adenohypophysis, the adrenal medulla, and Leydig cells) expressed the protein strongly and diffusely. The spermatic epithelium of the testis expressed the protein moderately. A characteristic immunostaining was observed in Hassall's corpuscles of the thymus, oxyphilic cells of the thyroid and parathyroid glands, and chondrocytes. Comparing these results with those of hK6, we observed that both kallikreins had a similar IHC expression pattern.

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“…Functionally, KLK1 is considered the major tissue kallikrein serine protease, which liberates bradykinin from LMW-kininogen (Clements 1997). In the rat, the greatest increase in tissue kallikrein is seen in the uterine glandular epithelium (Valdes et al 1996) and gene expression coincides with the period of trophoblast invasiveness (Chan et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The 13 porcine tissue kallikrein genes are clustered on chromosome 6 (Ferando et al 2006) and the pig lacks orthologs to human KLK2 and KLK3 as occurs in rodents . Tissue kallikreins are known to regulate the activation of many growth factors and extracellular proteases in a variety of tissues (Clements 1997). Expression for a number of the tissue kallikreins is regulated by androgens and estrogens, which contributes to tissue kallikrein expression in reproductive organs including the ovary, uterus, placenta, and mammary gland (Yousef & Diamandis 2001).…”

Section: Discussionmentioning

confidence: 99%

Porcine endometrial and conceptus tissue kallikrein 1, 4, 11, and 14 gene expression

Fernando¹,

Buck

Ashworth

et al. 2006

Reproduction

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Previous studies have suggested that the porcine endometrium may express several tissue kallikreins during the estrous cycle and early pregnancy. The present study investigated porcine endometrial and conceptus tissue kallikrein 1, 4, 11, and 14 mRNA expression during the estrous cycle and early pregnancy. Tissue kallikrein (KLK) gene expression was evaluated using quantitative RT-PCR and in situ hybridization. KLK1 expression was similar across the estrous cycle and early pregnancy, and localized to the endometrial luminal (L) and glandular (G) epithelium. KLK4 endometrial mRNA expression was greatest on days 0, 5, and 10 when compared with days 12, 15, and 17 of the estrous cycle and greater in cyclic compared with pregnant gilts. Expression of KLK4 was more intense in the stroma and uterine epithelium from days 0 to 10 of the estrous cycle. Endometrial KLK11 mRNA was not different between cyclic and pregnant gilts but the expression was greatest on days 10 and 12 compared with all other days evaluated. There was an increased intensity of KLK11 gene expression in the stratum compactum on day 10 of the estrous cycle and early pregnancy. Endometrial KLK14 mRNA expression was not detectable on days 5 and 10 but was expressed on days 0, 12, 15, and 17 of the estrous cycle and pregnancy. KLK14 expression was localized in the uterine L and G epithelium, and stroma throughout the endometrium after day 10. Conceptus KLK1 mRNA did not change from days 10 to 17 of gestation. However, conceptus KLK4, and 14 mRNA expression was greatest on day 10 with expression declining after day 14 of gestation. Expression of the various tissue kallikreins in the endometrium and conceptus during the estrous cycle and early pregnancy in the pig can serve in the activation of growth factors and tissue remodeling during the establishment of pregnancy. IntroductionPrior to initiating the epitheliochorial type of placental attachment to the uterine surface on day 13 of pregnancy, porcine conceptuses undergo rapid elongation from a 10 mm sphere to a long filamentous thread-like structure (Geisert et al. 1982, Stroband & Van de Lende 1990. Following trophoblast elongation, attachment to the uterine surface epithelium by the developing conceptuses stimulates a localized increase in transcapillary transport (Keys & King 1990) and uterine blood flow (Ford et al. 1982), which occurs concurrently with the establishment and maintenance of pregnancy (Geisert & Yelich 1997). The increase in uterine blood flow and many of the endometrial responses that occur during early porcine conceptus development resembles the acute-phase response induced during tissue inflammation (Salier et al. 1996, Geisert & Yelich 1997.The tissue kallikrein family of serine proteases activate a wide range of substrates and growth factors (Chan et al. 1999), suggesting that kallikreins are involved in many integral processes of early embryonic development, such as regulation of uterine blood flow, angiogenesis, tissue invasion, and mitogenesis . Five tissue kallikrein...

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The Molecular Biology of the Kallikreins and their Roles in Inflammation

Cited by 48 publications

References 263 publications

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Identification and Characterization of KLK-L4, a New Kallikrein-like Gene That Appears to be Down-regulated in Breast Cancer Tissues

Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

Porcine endometrial and conceptus tissue kallikrein 1, 4, 11, and 14 gene expression

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