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Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas.
Clin Cancer Res 2001; 7(8):2363-71CC

Abstract

Previous studies indicated that a new member of the human kallikrein (KLK) gene family, KLK4, was expressed in prostate, breast, and endometrial carcinoma cell lines and may have potential as a tumor marker. The aim of this study was to examine the expression of KLK4 in the normal ovary and ovarian tumors of different histology, stage, and differentiation and to determine its association with ovarian tumor progression. Using reverse transcription-PCR, Southern blot, and densitometry analyses, we found the level of KLK4 expression was higher in late stage serous (SER) epithelial-derived ovarian carcinomas than in normal ovaries, mucinous epithelial tumors, and granulosa cell tumors. KLK4 was highly expressed in all of the SER ovarian carcinoma cell lines (eight of eight), SER epithelial carcinomas (11 of 11), and two adenomas, whereas it was expressed at a lower level (or not at all) in normal ovaries (four of six), mucinous epithelial tumors (three of four), endometrioid carcinomas (four of five), clear cell carcinomas (two of three), or granulosa cell tumors (three of six). Of particular interest, KLK4 mRNA variants were detected in SER ovarian carcinoma cell lines and primary cultured ovarian tumor cells, but they were not present in normal ovaries. In situ hybridization analysis showed that KLK4 mRNA transcripts are localized to adenocarcinoma cells of ovarian tumor tissues. Similarly, immunohistochemical staining of ovarian carcinoma sections showed immunoreactivity to KLK4 protein product (hK4) antipeptide antibodies. In addition, intracellular hK4 levels, as detected on Western blot analysis, were induced by 100 nM estrogen treatment of the estrogen receptor positive ovarian carcinoma cell line OVCAR-3, >8-24 h. Our results show that the level of KLK4 expression and expression of KLK4 mRNA variants are associated with progression of ovarian cancer, particularly late stage SER adenocarcinomas. Moreover, hK4 may be a candidate marker for the diagnosis and/or monitoring of ovarian epithelial carcinomas.

Authors+Show Affiliations

Centre of Molecular Biotechnology, School of Life Sciences, Queensland University of Technology, Brisbane, Queensland 4001, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11489814

Citation

Dong, Y, et al. "Human Kallikrein 4 (KLK4) Is Highly Expressed in Serous Ovarian Carcinomas." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 7, no. 8, 2001, pp. 2363-71.
Dong Y, Kaushal A, Bui L, et al. Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. Clin Cancer Res. 2001;7(8):2363-71.
Dong, Y., Kaushal, A., Bui, L., Chu, S., Fuller, P. J., Nicklin, J., ... Clements, J. A. (2001). Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 7(8), pp. 2363-71.
Dong Y, et al. Human Kallikrein 4 (KLK4) Is Highly Expressed in Serous Ovarian Carcinomas. Clin Cancer Res. 2001;7(8):2363-71. PubMed PMID: 11489814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. AU - Dong,Y, AU - Kaushal,A, AU - Bui,L, AU - Chu,S, AU - Fuller,P J, AU - Nicklin,J, AU - Samaratunga,H, AU - Clements,J A, PY - 2001/8/8/pubmed PY - 2001/10/19/medline PY - 2001/8/8/entrez SP - 2363 EP - 71 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 7 IS - 8 N2 - Previous studies indicated that a new member of the human kallikrein (KLK) gene family, KLK4, was expressed in prostate, breast, and endometrial carcinoma cell lines and may have potential as a tumor marker. The aim of this study was to examine the expression of KLK4 in the normal ovary and ovarian tumors of different histology, stage, and differentiation and to determine its association with ovarian tumor progression. Using reverse transcription-PCR, Southern blot, and densitometry analyses, we found the level of KLK4 expression was higher in late stage serous (SER) epithelial-derived ovarian carcinomas than in normal ovaries, mucinous epithelial tumors, and granulosa cell tumors. KLK4 was highly expressed in all of the SER ovarian carcinoma cell lines (eight of eight), SER epithelial carcinomas (11 of 11), and two adenomas, whereas it was expressed at a lower level (or not at all) in normal ovaries (four of six), mucinous epithelial tumors (three of four), endometrioid carcinomas (four of five), clear cell carcinomas (two of three), or granulosa cell tumors (three of six). Of particular interest, KLK4 mRNA variants were detected in SER ovarian carcinoma cell lines and primary cultured ovarian tumor cells, but they were not present in normal ovaries. In situ hybridization analysis showed that KLK4 mRNA transcripts are localized to adenocarcinoma cells of ovarian tumor tissues. Similarly, immunohistochemical staining of ovarian carcinoma sections showed immunoreactivity to KLK4 protein product (hK4) antipeptide antibodies. In addition, intracellular hK4 levels, as detected on Western blot analysis, were induced by 100 nM estrogen treatment of the estrogen receptor positive ovarian carcinoma cell line OVCAR-3, >8-24 h. Our results show that the level of KLK4 expression and expression of KLK4 mRNA variants are associated with progression of ovarian cancer, particularly late stage SER adenocarcinomas. Moreover, hK4 may be a candidate marker for the diagnosis and/or monitoring of ovarian epithelial carcinomas. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/11489814/Human_kallikrein_4__KLK4__is_highly_expressed_in_serous_ovarian_carcinomas_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11489814 DB - PRIME DP - Unbound Medicine ER -