Human Kallikrein 4 (KLK4) Is Highly Expressed in Serous Ovarian Carcinomas
Dong, Ying, Kaushal, Aneel, Chu, Simon, Bui, Loan T., Fuller, Peter J., Nicklin, Jim, Samaratunga, Hemamali, & Clements, Judith A. (2001) Human Kallikrein 4 (KLK4) Is Highly Expressed in Serous Ovarian Carcinomas. Clinical Cancer Research, 7(8), pp. 2363-2371.
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.
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|Item Type:||Journal Article|
|Additional Information:||Articles free to read on journal website after 12 months|
|Divisions:||Past > QUT Faculties & Divisions > Faculty of Science and Technology|
|Copyright Owner:||Copyright 2001 American Association for Cancer Research|
|Deposited On:||24 Sep 2007|
|Last Modified:||31 Mar 2015 07:51|
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