Expression of the serine protease kallikrein 7 and its inhibitor antileukoprotease is decreased in prostate cancer

Arch Pathol Lab Med. 2008 Nov;132(11):1796-801. doi: 10.5858/132.11.1796.

Abstract

Context: Kallikreins are a subgroup of serine proteases with diverse physiologic functions. It has been confirmed that kallikrein 7 (KLK7) is differentially expressed in ovarian and breast cancer. Antileukoprotease (ALP) has been shown to be a specific inhibitor of human kallikrein 7 (hK7). Antileukoprotease overexpression is commonly associated with aggressive, high-risk, or metastatic cancer originating from various organs.

Objective: To investigate the expression and potential role of hK7 and its inhibitor ALP in prostate cancer.

Design: The mRNA expression of KLK7 and ALP transcript in benign prostate epithelial cells and prostate cancers was evaluated by semiquantitative reverse transcription-polymerase chain reaction. We examined hK7 and ALP protein expression by immunohistochemistry in 20 normal prostate tissues, 50 benign prostatic hyperplasia tissues, and 103 prostate cancers. Western blot examination showed protein expression of hK7 and ALP in benign prostate epithelial cells and prostate cancer cell lines.

Results: Semiquantitative polymerase chain reaction examination revealed that the mRNA level of KLK7 and ALP was significantly decreased in prostate cancers compared with that in benign prostate epithelial cells (P < .001). Immunohistochemical expression of hK7 was observed in prostate epithelial cells, whereas little or no staining was observed in prostate cancer. Western blot analysis revealed that hK7 and ALP were decreased in malignant prostate epithelium.

Conclusions: Like hK7, ALP is down-regulated in prostate cancers, which begs the question of whether it remains an effective inhibitor of hK7 or whether it is discordant in time or space and is ineffective as an inhibitor of hK7. The function of KLK7 and ALP in prostate cancer should be further studied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Down-Regulation
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Kallikreins / genetics
  • Kallikreins / metabolism*
  • Male
  • Prostate / cytology
  • Prostate / metabolism
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Secretory Leukocyte Peptidase Inhibitor / genetics
  • Secretory Leukocyte Peptidase Inhibitor / metabolism*

Substances

  • RNA, Messenger
  • Secretory Leukocyte Peptidase Inhibitor
  • KLK7 protein, human
  • Kallikreins