Prostate-specific antigen, its molecular forms, and other kallikrein markers for detection of prostate cancer

Stephan, Carsten; Jung, Klaus; Diamandis, Eleftherios P.; Rittenhouse, Harry G.; Lein, Michael; Loening, Stefan A.

doi:10.1016/s0090-4295(01)01449-2

Cited by 68 publications

(50 citation statements)

References 45 publications

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“…10 Another emerging prostatic biomarker is human glandular kallikrein 2 (hK2). [11][12][13][14][15] More recently, a few other members of the kallikrein family, such as hK4 and hK15 16,17 have also been shown to have potential as prostatic biomarkers. Human kallikrein 11 (hK11) appears to be a promising new biomarker for prostatic and ovarian carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues

et al. 2003

Prostate Cancer Prostatic Dis

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Human kallikreins 6, 10 and 13 (hK6, hK10 and hK13) are expressed by many normal, mainly glandular tissues, including prostatic epithelium. Some kallikreins may function as tumor suppressors or are downregulated during cancer progression. The aim of this study was to evaluate the immunoexpression of these kallikreins in benign and malignant prostatic tissues and correlate their expression with prostate cancer (PC) prognosis. Included in the study were 25 cases of nonmalignant prostate and 179 cases of PC. Among them, 122 PC cases were immunostained for hK6, 94 for hK10 and 113 for hK13, respectively. The follow-up period for a subset of 68 patients who had undergone radical prostatectomy (RP) was 1-58 months (mean ¼ 13.471.7 and median ¼ 8.0 months). A cutoff value of 0.2 lg/l of serum PSA was established as a biochemical recurrence threshold. Follow-up information was available for 26/55 RP cases stained for hK6, 14/32 cases stained for hK10 and 25/59 cases stained for hK13. Gleason score (GS) 7 carcinomas were stratified as 7a and 7b, according to the primary grade. PC with GS 2-7a were histologically categorized as low malignant (LM) and PC with GS 7b-10 as high malignant (HM). The immunohistochemical method of streptavidinbiotin-peroxidase using monoclonal and polyclonal antibodies was performed. In the benign prostate and in prostatic intraepithelial neoplasia, a cytoplasmic immunostaining of varying intensity was evident. In PC, the immunoexpression of all kallikreins was decreased: 102/122 cases (84%) were positive for hK6, 73/94 (78%) for hK10 and 97/113 (86%) for hK13, respectively. A statistically significant difference in expression was found, in comparison to nonmalignant prostates (P ¼ 0.029, 0.009 and 0.045, respectively). Also, a positive correlation was observed between the immunoexpression of these three kallikreins. Concerning the histological grade, HM-PC expressed all three kallikreins with a slightly higher percentage than LM-PC: 79 vs 88% for hK6, 76 vs 79% for hK10 and 76 vs 92% for hK13. These differences were statistically significant only in the case of hK13 (P ¼ 0.024). Serum PSA did not correlate with kallikrein immunoexpression in PC. Furthermore, there was no significant correlation between kallikrein expression and pathological stage or recurrence, in the cases of RP. All three kallikreins are expressed in the nonmalignant and malignant prostate, with cancer tissues demonstrating slightly lower expression. Expression levels did not correlate with aggressiveness and they do not seem to have value for prostate cancer prognosis.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues

et al. 2003

Prostate Cancer Prostatic Dis

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“…Recent studies have begun to identify androgen-regulated and prostate-enriched genes and the proteins that they encode which started to define the molecular details of androgen action in the prostate and in prostate carcinogenesis. The best known of these genes is Kallikrein 3 (KLK3), also called prostate-specific antigen (PSA), that is a widely used clinical tumor marker for detection and monitoring of prostate cancer progression (Stephan et al, 2002). Other androgenregulated genes that are primarily expressed in the prostate include KLK2 (Rittenhouse et al, 1998), KLK4 (Nelson et al, 1999;Stephenson et al, 1999;Yousef et al, 1999;Korkmaz et al, 2001), NKX3.1 (Bieberich et al, 1996;He et al, 1997), and PCGEM (Srikantan et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer

et al. 2005

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We have identified a novel gene, six transmembrane protein of prostate 2 (STAMP2), named for its high sequence similarity to the recently identified STAMP1 gene. STAMP2 displays a tissue-restricted expression with highest expression levels in placenta, lung, heart, and prostate and is predicted to code for a 459-amino acid six transmembrane protein. Using a form of STAMP2 labeled with green flourescent protein (GFP) in quantitative time-lapse and immunofluorescence confocal microscopy, we show that STAMP2 is primarily localized to the Golgi complex, trans-Golgi network, and the plasma membrane. STAMP2 also localizes to vesicular-tubular structures in the cytosol and colocalizes with the Early Endosome Antigen1 (EEA1) suggesting that it may be involved in the secretory/endocytic pathways. STAMP2 expression is exquisitely androgen regulated in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptornegative prostate cancer cell lines PC-3 and DU145. Analysis of STAMP2 expression in matched normal and tumor samples microdissected from prostate cancer specimens indicates that STAMP2 is overexpressed in prostate cancer cells compared with normal prostate epithelial cells. Furthermore, ectopic expression of STAMP2 in prostate cancer cells significantly increases cell growth and colony formation suggesting that STAMP2 may have a role in cell proliferation. Taken together, these data suggest that STAMP2 may contribute to the normal biology of the prostate cell, as well as prostate cancer progression.

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“…Recent studies have begun to identify androgen-regulated and prostate-enriched genes and the proteins that they encode, which started to define the molecular details of androgen action in the prostate and in prostate carcinogenesis. The best known of these genes is KLK3, also called prostate-specific antigen (PSA), that is a widely used clinical tumor marker for detection and monitoring of prostate cancer progression (2). Another gene that is androgen regulated and highly enriched to prostate for expression is KLK2, which may also have utility as a prostate cancer marker in conjunction with PSA (3).…”

Section: Introductionmentioning

confidence: 99%

Kallikrein 4 is a Predominantly Nuclear Protein and Is Overexpressed in Prostate Cancer

et al. 2004

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Kallikreins (KLKs) are highly conserved serine proteases that play key roles in a variety of physiological and pathological processes. KLKs are secreted proteins that have extracellular substrates and function. For example, prostate-specific antigen (or KLK3) is a secreted protein that is widely used as a diagnostic marker for prostate cancer. KLK4 is a recently identified member of the kallikrein family that is regulated by androgens and is highly specific to prostate for expression. Here, we show that the gene product of KLK4, hK4, is the first member of the KLK family that is intracellularly localized. We provide strong evidence that the previously assigned first exon that was predicted to code for a signal peptide that would target hK4 for secretion is not part of the physiologically relevant form of KLK4 mRNA. In addition to detailed mapping of the KLK4 mRNA 5 end by RT-PCR, this conclusion is supported by predominantly nuclear localization of the hK4 protein in the cell, documented by both immunofluorescence and cell fractionation experiments. Furthermore, in addition to androgens, hK4 expression is regulated by estrogen and progesterone in prostate cancer cells. Finally, in situ hybridization on normal and hyperplastic prostate samples in tissue microarrays indicate that KLK4 is predominantly expressed in the basal cells of the normal prostate gland and overexpressed in prostate cancer. These data suggest that KLK4 has a unique structure and function compared with other members of the KLK family and may have a role in the biology and characterization of prostate cancer.

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Prostate-specific antigen, its molecular forms, and other kallikrein markers for detection of prostate cancer

Cited by 68 publications

References 45 publications

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues

Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer

Kallikrein 4 is a Predominantly Nuclear Protein and Is Overexpressed in Prostate Cancer

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