Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis

Partin, Alan W.; Catàlona, William J.; Finlay, Jessica; Darte, Claude; Tindall, Donald J.; Young, Charles Y.F.; Klee, George G.; Chan, Daniel W.; Rittenhouse, Harry G.; Wolfert, Robert L.; Woodrum, David L.

doi:10.1016/s0090-4295(99)00270-8

Cited by 123 publications

(64 citation statements)

References 26 publications

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“…These genes include the AR, PSA (kallikrein 3) as previously reported (15), Kallikrein 2, POV-1, TMPRSS2, and prostate-derived factor. The kallikrein 2 gene is regulated by AR and being evaluated as a marker for prostate cancer progression (25). The POV-1 gene encodes a transcript for an L amino acid transporter (26) that is up-regulated in aggressive prostate carcinoma (27).…”

Section: Ectopic Expression Of Ebp1 Down-regulates Androgen-regulatedmentioning

confidence: 99%

The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells

Zhang

Wang

Jelovac

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

101

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Down-regulation of the androgen receptor (AR) is being evaluatedas an effective therapy for the advanced stages of prostate cancer. We report that Ebp1, a protein identified by its interactions with the ErbB3 receptor, down-regulates expression of AR and ARregulated genes in the LNCaP prostate cancer cell line. Using microarray analysis, we identified six endogenous AR target genes, including the AR itself, that are down-regulated by ebp1 overexpression. Chromatin immunoprecipitation assays revealed that Ebp1 was recruited to the prostate-specific antigen gene promoter in response to the androgen antagonist bicalutamide, suggesting that Ebp1 directly affected the expression of AR-regulated genes in response to androgen antagonists. Ebp1 expression was reduced in cells that had become androgen-independent. Androgens failed to stimulate either the growth of ebp1 transfectants or transcription of AR-regulated reporter genes in these cells. The agonist activity of the antiandrogen cyproterone acetate was abolished in ebp1 transfectants. In severe combined immunodeficient mice, Ebp1 overexpression resulted in a reduced incidence of LNCaP tumors and slower tumor growth. These findings suggest that Ebp1 is a previously unrecognized therapeutic target for treatment of hormone refractory prostate cancer.ErbB receptors ͉ transcriptional corepressors ͉ androgen independence

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Section: Ectopic Expression Of Ebp1 Down-regulates Androgen-regulatedmentioning

confidence: 99%

The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells

Zhang

Wang

Jelovac

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

101

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“…This has led to the development of highly specific antibodies for selective immunodetection of free (fPSA) and complexed PSA, [6][7][8] human kallikrein-related peptidase 2 (hK2 or KLK2) 9,10 and various fPSA-subfractions. 11,12 Clinical testing of free and complexed PSA has significantly enhanced cancer specificity over the testing of tPSA alone.…”

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confidence: 99%

“…Serum levels of hk2 and various fPSAsubfractions have been reported to differ significantly in benign vs. malignant prostatic disease. [9][10][11][12] Moreover, it is implicated that a combination of these measurements with free or tPSA show significant potential to further improve discrimination of cancer from noncancer subjects in referral and screening cohorts.…”

mentioning

confidence: 99%

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Steuber

Vickers

Haese

et al. 2007

Intl Journal of Cancer

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Clinicians currently use simple cut-points, such as serum prostatespecific antigen (PSA) 4 ng/ml, to decide whether to recommend further work-up for prostate cancer (PCa). As an alternative strategy, we evaluated multivariable models giving probabilities of a PCa diagnosis based on PSA and several circulating novel biomarkers. We measured total PSA, free PSA (fPSA), fPSA subfractions (single-chain fPSA-I and multichain fPSA-N), total human glandular kallikrein 2 (hK2) and full-length and cleaved forms of soluble urokinase plasminogen activator receptor (suPAR) in pretreatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a ''base'' regression model to predict biopsy outcome. We then compared this base model to models supplemented by various combinations of circulating markers, using concordance index (AUC) to measure diagnostic discrimination. PCa prediction was significantly enhanced by models supplemented by measurements of suPAR fragments and fPSA isoforms. Addition of these markers improved bootstrap-corrected AUC from 0.611 for a cut-point and 0.706 for the base model to 0.754 for the full model (p 5 0.005). This improved diagnostic accuracy was also seen in subanalysis of patients with PSA 2-9.99 ng/ml and normal findings on DRE (0.652 vs. 0.715, p 5 0.039). In this setting, hK2 did not add diagnostic information. Measurements of individual forms of suPAR and PSA isoforms contributed significantly to discrimination of men with PCa from those with no evidence of malignancy. ' 2006 Wiley-Liss, Inc.

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“…Recently another member of the human kallikrein family, human kallikrein 2 (hK2), has shown promise as a diagnostic marker for prostate cancer. [1][2][3] hK2 and PSA share 80% amino acid identity, are both expressed predominantly in the prostate and are androgen-regulated. hK2 and PSA are both secreted as zymogen, proenzyme forms and are converted to mature enzymatically active enzymes extracellularly.…”

mentioning

confidence: 99%

Human kallikrein 2 (hK2), but not prostate‐specific antigen (PSA), rapidly complexes with protease inhibitor 6 (PI‐6) released from prostate carcinoma cells

Saedi

Zhu²,

Marker³

et al. 2001

Int. J. Cancer

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Human kallikrein 2 (hK2) is a secreted, trypsin-like protease that shares 80% amino acid sequence identity with prostate-specific antigen (PSA). hK2 has been shown to be a serum marker for prostate cancer and may also play a role in cancer progression and metastasis. We have previously identified a novel complex between human kallikrein 2 (hK2) and protease inhibitor 6 (PI-6) in prostate cancer tissue. PI-6 is an intracellular serine protease inhibitor with both antitrypsin and antichymotrypsin activity. In the current study we have shown that PI-6 forms a rapid in vitro complex with hK2 but does not complex with PSA. Recombinant mammalian cells expressing both hK2 and PI-6 showed hK2-PI-6 complex in the spent media only after cell death and lysis. Similarly, LNCaP cells expressing endogenous hK2 and PI-6 showed extracellular hK2-PI-6 complex formation concurrently with cell death. Immunostaining of prostate cancer tissues with PI-6 monoclonal antibodies showed a marked preferential staining pattern in cancerous epithelial cells compared with noncancerous tissue. These results indicate that the hK2-PI-6 complex may be a naturally occurring marker of tissue damage and necrosis associated with neoplasia. Both hK2 and PI-6 were shed into the lumen of prostate cancer glands as granular material that appeared to be cellular necrotic debris. The differential staining pattern of PI6 in tissues suggests a complex regulation of PI-6 expression that may play a role in other aspects of neoplastic progression.

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Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis

Cited by 123 publications

References 26 publications

The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells

The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells

Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy

Human kallikrein 2 (hK2), but not prostate‐specific antigen (PSA), rapidly complexes with protease inhibitor 6 (PI‐6) released from prostate carcinoma cells

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