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Expression and Functional Significance of HtrA1 Loss in Endometrial Cancer
- Publication Year :
- 2010
-
Abstract
- Purpose: The purpose of this study was to determine if loss of serine protease HtrA1 in endometrial cancer will promote the invasive potential of EC cell lines. Experimental design: Western blot analysis and immunohistochemistry methods were used to determine HtrA1 expression in EC cell lines and primary tumors, respectively. Migration, invasion assays and in vivo xenograft experiment were performed to compare the extent of metastasis between HtrA1 expressing and HtrA1 knocked down clones. Results: Western blot analysis of HtrA1 in 13 EC cell lines revealed complete loss of HtrA1 expression in all seven papillary serous EC cell lines. Downregulation of HtrA1 in Hec1A and Hec1B cell lines resulted in a three- to fourfold increase in the invasive potential. Exogenous expression of HtrA1 in Ark1 and Ark2 cells resulted in three- to fourfold decrease in both invasive and migration potential of these cells. There was an increased rate of metastasis to the lungs associated with HtrA1 downregulation in Hec1B cells compared to control cells with endogenous HtrA1 expression. Enhanced expression of HtrA1 in Ark2 cells resulted in significantly less tumor nodules metastasizing to the lungs compared to parental or protease deficient (SA mutant) Ark2 cells. Immunohistochemical analysis showed 57% (105/184) of primary EC tumors had low HtrA1 expression. The association of low HtrA1 expression with high-grade endometrioid tumors was statistically significant (P = 0.016). Conclusions: Collectively, these data indicate loss of HtrA1 may contribute to the aggressiveness and metastatic ability of endometrial tumors. Clin Cancer Res; 17(3); 427–36. ©2010 AACR.
- Subjects :
- Cancer Research
Lung Neoplasms
Down-Regulation
Endogeny
Mice, SCID
Biology
Article
Metastasis
Mice
Western blot
Downregulation and upregulation
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Aged
medicine.diagnostic_test
Endometrial cancer
Serine Endopeptidases
High-Temperature Requirement A Serine Peptidase 1
Middle Aged
medicine.disease
eye diseases
Endometrial Neoplasms
Oncology
Cell culture
Cancer research
Immunohistochemistry
Female
Neoplasm Transplantation
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b43e9dd136ce7167bccbf2e2d8be824a