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Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers.
Clin Cancer Res 2003; 9(5):1710-20CC

Abstract

PURPOSE

The wild-type or variant mRNAs of several kallikrein (KLK) genes, such as KLK4, are highly expressed in ovarian carcinomas and may have potential as tumor markers. Two of these KLK genes (KLK5 and KLK7) and their proteins (hK5 and hK7) were first identified in the skin epidermis, where hK5 may be the physiological activator of hK7. The purpose of this study was to reexamine the expression of KLK5/hK5 and KLK7/hK7 and their association and to determine whether cancer-related variant transcripts were expressed.

EXPERIMENTAL DESIGN

The expression of KLK5/hK5 and KLK7/hK7 was analyzed in the same cohort (n = 37) of benign (n = 4) and malignant ovarian tissue (n = 23) samples and primary cultured cells (n = 21) and in 8 ovarian cancer cell lines using semiquantitative RT-PCR; Southern, Northern, and Western blot analyses; and immunohistochemistry techniques.

RESULTS

We showed the concordant higher expression of both KLK5/hK5 and KLK7/hK7 in ovarian carcinomas, especially late-stage serous carcinomas, compared with normal ovaries and benign adenomas. We also found that one novel KLK5 transcript with a short 5'-untranslated region and a novel KLK7 transcript with a long 3'-untranslated region were highly expressed in the ovarian cancer cell lines OVCAR-3 and PEO1, respectively, but were expressed at very low levels in normal ovarian epithelial cells. Both Western blot and immunohistochemistry analyses showed that these two enzymes are secreted from ovarian carcinoma cells.

CONCLUSIONS

Our study demonstrated that hK5 and hK7, or more specifically, the short KLK5 and long KLK7 transcripts, may be useful as tumor markers for epithelial-derived serous carcinomas. However, additional clinical studies assessing serum levels of these putative biomarkers are required to confirm their usefulness in the diagnosis and/or monitoring of these tumors.

Authors+Show Affiliations

The Center of Molecular Biotechnology, School of Life Sciences, Queensland University of Technology, Brisbane, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12738725

Citation

Dong, Ying, et al. "Differential Splicing of KLK5 and KLK7 in Epithelial Ovarian Cancer Produces Novel Variants With Potential as Cancer Biomarkers." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 9, no. 5, 2003, pp. 1710-20.
Dong Y, Kaushal A, Brattsand M, et al. Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. Clin Cancer Res. 2003;9(5):1710-20.
Dong, Y., Kaushal, A., Brattsand, M., Nicklin, J., & Clements, J. A. (2003). Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 9(5), pp. 1710-20.
Dong Y, et al. Differential Splicing of KLK5 and KLK7 in Epithelial Ovarian Cancer Produces Novel Variants With Potential as Cancer Biomarkers. Clin Cancer Res. 2003;9(5):1710-20. PubMed PMID: 12738725.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. AU - Dong,Ying, AU - Kaushal,Aneel, AU - Brattsand,Maria, AU - Nicklin,Jim, AU - Clements,Judith A, PY - 2003/5/10/pubmed PY - 2004/1/13/medline PY - 2003/5/10/entrez SP - 1710 EP - 20 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 9 IS - 5 N2 - PURPOSE: The wild-type or variant mRNAs of several kallikrein (KLK) genes, such as KLK4, are highly expressed in ovarian carcinomas and may have potential as tumor markers. Two of these KLK genes (KLK5 and KLK7) and their proteins (hK5 and hK7) were first identified in the skin epidermis, where hK5 may be the physiological activator of hK7. The purpose of this study was to reexamine the expression of KLK5/hK5 and KLK7/hK7 and their association and to determine whether cancer-related variant transcripts were expressed. EXPERIMENTAL DESIGN: The expression of KLK5/hK5 and KLK7/hK7 was analyzed in the same cohort (n = 37) of benign (n = 4) and malignant ovarian tissue (n = 23) samples and primary cultured cells (n = 21) and in 8 ovarian cancer cell lines using semiquantitative RT-PCR; Southern, Northern, and Western blot analyses; and immunohistochemistry techniques. RESULTS: We showed the concordant higher expression of both KLK5/hK5 and KLK7/hK7 in ovarian carcinomas, especially late-stage serous carcinomas, compared with normal ovaries and benign adenomas. We also found that one novel KLK5 transcript with a short 5'-untranslated region and a novel KLK7 transcript with a long 3'-untranslated region were highly expressed in the ovarian cancer cell lines OVCAR-3 and PEO1, respectively, but were expressed at very low levels in normal ovarian epithelial cells. Both Western blot and immunohistochemistry analyses showed that these two enzymes are secreted from ovarian carcinoma cells. CONCLUSIONS: Our study demonstrated that hK5 and hK7, or more specifically, the short KLK5 and long KLK7 transcripts, may be useful as tumor markers for epithelial-derived serous carcinomas. However, additional clinical studies assessing serum levels of these putative biomarkers are required to confirm their usefulness in the diagnosis and/or monitoring of these tumors. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/12738725/Differential_splicing_of_KLK5_and_KLK7_in_epithelial_ovarian_cancer_produces_novel_variants_with_potential_as_cancer_biomarkers_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12738725 DB - PRIME DP - Unbound Medicine ER -