Expression of the Serine Protease Kallikrein 7 and Its Inhibitor Antileukoprotease Is Decreased in Prostate Cancer

Document Sample
Expression of the Serine Protease Kallikrein 7 and Its Inhibitor Antileukoprotease Is Decreased in Prostate Cancer Powered By Docstoc
					     Expression of the Serine Protease Kallikrein 7 and Its
         Inhibitor Antileukoprotease Is Decreased in
                        Prostate Cancer
          Qiang Xuan, MD; Xiaoli Yang, MD; Linjian Mo, MD; Fengyu Huang, MD; Youhong Pang, MD; Min Qin, MD;
                           Zhiqiang Chen, MD; Min He, MD; Qi Wang, MD; Zeng-Nan Mo, MD

● Context.—Kallikreins are a subgroup of serine proteases                  showed protein expression of hK7 and ALP in benign pros-
with diverse physiologic functions. It has been confirmed                   tate epithelial cells and prostate cancer cell lines.
that kallikrein 7 (KLK7 ) is differentially expressed in ovar-                Results.—Semiquantitative polymerase chain reaction
ian and breast cancer. Antileukoprotease (ALP) has been                    examination revealed that the mRNA level of KLK7 and
shown to be a specific inhibitor of human kallikrein 7                      ALP was significantly decreased in prostate cancers com-
(hK7). Antileukoprotease overexpression is commonly as-                    pared with that in benign prostate epithelial cells (P
sociated with aggressive, high-risk, or metastatic cancer                  .001). Immunohistochemical expression of hK7 was ob-
                                                                           served in prostate epithelial cells, whereas little or no stain-
originating from various organs.
                                                                           ing was observed in prostate cancer. Western blot analysis
   Objective.—To investigate the expression and potential
                                                                           revealed that hK7 and ALP were decreased in malignant
role of hK7 and its inhibitor ALP in prostate cancer.                      prostate epithelium.
   Design.—The mRNA expression of KLK7 and ALP tran-                          Conclusions.—Like hK7, ALP is down-regulated in pros-
script in benign prostate epithelial cells and prostate can-               tate cancers, which begs the question of whether it re-
cers was evaluated by semiquantitative reverse transcrip-                  mains an effective inhibitor of hK7 or whether it is discor-
tion–polymerase chain reaction. We examined hK7 and                        dant in time or space and is ineffective as an inhibitor of
ALP protein expression by immunohistochemistry in 20                       hK7. The function of KLK7 and ALP in prostate cancer
normal prostate tissues, 50 benign prostatic hyperplasia tis-              should be further studied.
sues, and 103 prostate cancers. Western blot examination                      (Arch Pathol Lab Med. 2008;132:1796–1801)


T   he extracellular matrix proteolysis accompanying tu-
     mor invasion and metastasis is a highly complicated
process and probably involves a cascade of events requir-
                                                                           that hK7 may degrade adhesive interactions between in-
                                                                           dividual corneocytes in the stratum corneum that are the
                                                                           primary substrate for cellular desquamation or skin shed-
ing a variety of proteases.1 In this process, protease plays               ding.5 The fact that inhibition of hK7 prevents normal des-
a central role in paving the way for spreading tumor cells.                quamation of skin cells suggested that hK7 may represent
The human kallikrein gene family is a subfamily of serine                  a potential therapeutic target to inhibit the spread or me-
proteases and is located at chromosome locus 19q13.3-                      tastasis of carcinoma cells. Whether hK7 has a similar
q13.4. In recent years, 15 of the tissue kallikrein family                 function in prostate is worth studying.
genes have been identified and cloned. Human kallikrein                       Antileukoprotease (ALP), also known as secretory leu-
7 (hK7) was first found in the human stratum corneum                        kocyte proteinase inhibitor, has been identified as a potent
and with a possible involvement in desquamation.2 There                    inhibitor of leukocyte chymotrypsin, trypsin, elastase, and
is now increasing evidence that many kallikrein family                     cathepsin G6 and plays a significant role in protection
genes are related to human malignancies.3,4 We have found                  against neutrophil proteases during inflammatory re-
kallikrein 7 (KLK7) was upregulated in prostate epithelial                 sponses.7,8 The hK7-dependent desquamation of skin cells
cells cocultured with prostate fibroblasts compared with                    can be inhibited by ALP.9 This serine protease inhibitor is
epithelial cells cultured separately. It has been suggested                produced and released into mucus by secretory cells in
                                                                           the prostate, parotid, bronchus, cervix, and testis.6 Anti-
                                                                           leukoprotease has a local protective function against pro-
  Accepted for publication April 15, 2008.
  From the Institute of Urology, the First Affiliated Hospital (Drs Xuan,   teolytic degradation of the male reproductive tract tis-
Yang, L. Mo, Huang, Pang, Qin, Chen, and Z.-N. Mo), the Laboratory         sues10 and cervical gland. Several studies have reported
Center For Medical Science (Dr He), and the Affiliated Tumor Hospital       increased ALP expression in ovarian cancer tissues and in
(Dr Wang), Guangxi Medical University, Nanning, China                      the serum of patients with non–small cell lung cancer.11–13
  The authors have no relevant financial interest in the products or        Shigemasa et al14 also have identified that ALP, a peptide
companies described in this article.
  Reprints: Zeng-Nan Mo, MD, Institute of Urology, The First Affiliated     inhibitor of hK7, is highly overexpressed in ovarian tumor
Hospital of Guangxi M
				
DOCUMENT INFO
Description: 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.
BUY THIS DOCUMENT NOW PRICE: $6.95 100% MONEY BACK GUARANTEED
PARTNER ProQuest LLC
ProQuest creates specialized information resources and technologies that propel successful research, discovery, and lifelong learning.