A survey of alternative transcripts of human tissue kallikrein genes

Kurlender, Lisa; Borgoño, Carla A.; Michael, Iacovos P.; Obiezu, Christina V.; Elliott, Marc B.; Yousef, George M.; Diamandis, Eleftherios P.

doi:10.1016/j.bbcan.2005.02.001

Cited by 55 publications

(80 citation statements)

References 80 publications

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“…After sequencing, we confirmed this band to represent a previously identified splice variant (GenBank accession no. AY279383), which lacks exon 4 (Kurlender et al, 2005). Four benign and one normal ovarian tissue samples expressing low KLK6 were used as controls.…”

Section: Expression Of Klk6 Mrna Transcripts In Ovarian Tumoursmentioning

confidence: 99%

“…Some of these transcript variants have been shown to be specifically overexpressed in ovarian cancer (Dong et al, 2001(Dong et al, , 2003Magklara et al, 2001). KLK6 has four alternative transcripts encoding for the full-length KLK6 protein and four that may encode for truncated proteins (Kurlender et al, 2005). The longest KLK6 transcript (GenBank accession no.…”

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confidence: 99%

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Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

et al. 2007

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The human tissue kallikrein family (KLK for protein; KLK for gene) includes 15 members. Twelve kallikreins, including KLK6, are concurrently upregulated in ovarian cancer. However, the mechanism of this phenomenon remains unclear. In this study, we measured KLK6 expression in a large series of ovarian tissue cytosols and examined possible mechanisms of KLK6 up-regulation in ovarian cancer. Using a newly developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies, we quantified KLK6 expression in ovarian tissue cytosols, and confirmed the upregulation of KLK6 in ovarian cancer and its unfavourable prognostic value. We then examined KLK6 mRNA expression using reverse transcription -polymerase chain reaction and established its good concordance with KLK6 protein expression. This finding suggested that the KLK6 gene is under transcriptional regulation. We then scrutinised a few mechanisms that could explain KLK6 upregulation. The relative abundance of two KLK6 mRNA transcripts was studied; we found the same differential expression pattern in all samples, regardless of KLK6 levels. Genomic mutation screening of all exons and the 5 0 -flanking region of the KLK6 gene identified two linked single-nucleotide polymorphisms in the 5 0 -untranslated region, but neither correlated with KLK6 expression. Ovarian cell lines were separately treated with five steroid hormones. None of the treatments produced significant effects on KLK6 expression. We conclude that KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction.

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Section: Expression Of Klk6 Mrna Transcripts In Ovarian Tumoursmentioning

confidence: 99%

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confidence: 99%

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

et al. 2007

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“…This gene has five coding exons and one 5Ј-untranslated exon with at least four alternatively spliced forms known to date (21). All spliced forms are predicted to produce secreted proteins; however, the "classical" form of KLK12 (GenBank accession number NM_145894) is the only protein product that represents a typical kallikrein-like enzyme with expected serine protease activity.…”

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confidence: 99%

Kallikrein-related Peptidase 12 Hydrolyzes Matricellular Proteins of the CCN Family and Modifies Interactions of CCN1 and CCN5 with Growth Factors

Guillon-Munos

Οικονομοπούλου

Michel

et al. 2011

Journal of Biological Chemistry

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Kallikrein-related peptidases (KLKs) are an emerging group of secreted serine proteases involved in several physiological and pathological processes. We used a degradomic approach to identify potential substrates of KLK12. MDA-MB-231 cells were treated either with KLK12 or vehicle control, and the proteome of the overlying medium was analyzed by mass spectrometry. CCN1 (cyr61, ctgf, nov) was among the proteins released by the KLK12-treated cells, suggesting that KLK12 might be responsible for the shedding of this protein from the cell surface. Fragmentation of CCN1 by KLK12 was further confirmed in vitro, and the main cleavage site was localized in the hinge region between the first and second half of the recombinant protein. KLK12 can target all six members of the CCN family at different proteolytic sites. Limited proteolysis of CCNs (cyr61, ctgf, nov) was also observed in the presence of other members of the KLK family, such as KLK1, KLK5, and KLK14, whereas KLK6, KLK11, and KLK13 were unable to fragment CCNs. Because KLK12 seems to have a role in angiogenesis, we investigated the relations between KLK12, CCNs, and several factors known to be involved in angiogenesis. Solid phase binding assays showed that fragmentation of CCN1 or CCN5 by KLK12 prevents VEGF 165 binding, whereas it also triggers the release of intact VEGF and BMP2 from the CCN complexes. The KLK12-mediated release of TGF-␤1 and FGF-2, either as intact or truncated forms, was found to be concentration-dependent. These findings suggest that KLK12 may indirectly regulate the bioavailability and activity of several growth factors through processing of their CCN binding partners.

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“…The alternative splicing events imply exon skipping (mRNAs KLK8-T3, -T4, -T5, and -T6) and exon extension (KLK8-T2), which are the most common mechanisms generating mRNA variants in the KLK gene family (7,8 ). The KLK8 gene is much more active in NSCLC (P Ͻ 0.0001) than in healthy lung tissue, as it is for several other malignancies, including uterine endometrial carcinoma and ovarian and neck cancers (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

“…We have examined the prognostic value of alternative mRNA variants of the KLK8 6 (kallikrein-related peptidase 8) gene. This gene belongs to the kallikrein-related peptidase (KLK) gene family, which is both an exciting source of potential cancer biomarkers (6 ) and a mine of splice variants (7 ). The archetypical member of the KLK gene family is the KLK3 gene, which encodes the most widely recognized marker in urologic oncology, prostatespecific antigen (also known as KLK3).…”

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confidence: 99%

Alternative Splicing Variant of Kallikrein-Related Peptidase 8 as an Independent Predictor of Unfavorable Prognosis in Lung Cancer

et al. 2010

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A survey of alternative transcripts of human tissue kallikrein genes

Cited by 55 publications

References 80 publications

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

Kallikrein-related Peptidase 12 Hydrolyzes Matricellular Proteins of the CCN Family and Modifies Interactions of CCN1 and CCN5 with Growth Factors

Alternative Splicing Variant of Kallikrein-Related Peptidase 8 as an Independent Predictor of Unfavorable Prognosis in Lung Cancer

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