Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer

Bowden, Marissa A; Nezza-Cossens, Lisa L Di; Jobling, Tom; Salamonsen, Lois A.; Nie, Guiying

doi:10.1016/j.ygyno.2006.03.006

Cited by 83 publications

(67 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3) corresponding to the long and short isoforms of HtrA3; similar results were obtained previously for endometrial (9) and ovarian tissues (25). So far, two isoforms of HtrA3 produced through alternative splicing have been identified.…”

Section: -------------------------------------------------supporting

confidence: 85%

“…Recently, a work by Bowden et al (9) was published, in which the authors presented HtrA1 and HtrA3 downregulation in endometrial cancers. Moreover, it was shown that both HtrA1 and HtrA3 protein levels decreased with increasing grades of the cancer (9). In this study, we have shown the decrease of expression of HtrA1 and HtrA3 in a representative group of patients (n=124).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of HtrA1 was decreased in ovarian (7,8) and endometrial cancers (9), and in melanomas (10). It was shown that HtrA1 overexpression in melanoma cells inhibited proliferation and chemoinvasion while downregulation promoted cell proli-feration (10).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of human HtrA1, HtrA2, HtrA3 and TGF-β1 genes in primary endometrial cancer

et al. 2009

View full text Add to dashboard Cite

Abstract. The HtrA family of serine proteases takes part in cellular stress response including heat shock, inflammation and cancer. Downregulation of human HtrA1 and HtrA3 genes has been reported in some cancers, including endometrial cancer (EC), suggesting a tumor-suppressor role for both genes. The mechanism of the HtrA function is not known, however, evidence exists showing that both HtrA1 and HtrA3 regulate biological processes by modulating TGF-ß signaling. In the presented study the expression of human HtrA1, HtrA2, HtrA3 and TGF-ß1 genes was examined in 124 endometrial tissue specimens including 88 cancers and 36 normal endometria. The expression of the tested genes was evaluated at mRNA and protein levels by semi-quantitative RT-PCR and Western blotting methods, respectively. Our results showed significant decrease of HtrA1 and HtrA3 mRNA and protein levels in EC compared to normal tissues. The most dramatic decrease was found for HtrA3 at both mRNA and protein levels (3.2-and 5.6-fold, respectively). Moreover, the HtrA3 protein (short isoform) was not detected in 19% of the cancers, and its level decreased from the premenopausal to the postmenopausal group. The HtrA2 protein levels were significantly lower in EC tissues compared to normal tissues. We also found a significant increase of the TGF-ß1 protein level in EC as well as a significant negative correlation between HtrA1/2/3 and TGF-ß1 relative protein levels. Our results showing downregulation of HtrA1 and HtrA3 gene expression support previous studies suggesting a tumor suppressor role for these genes. Furthermore, our data suggest that HtrA2 may be involved in EC development as well as suggest the involvement of HtrA1, HtrA2 and HtrA3 in the inhibition of TGF-ß signaling in endometrial tissues.

show abstract

Section: -------------------------------------------------supporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of human HtrA1, HtrA2, HtrA3 and TGF-β1 genes in primary endometrial cancer

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The expression of HtrA1 and HtrA3 is decreased in several cancers, while overexpression of HtrA1 in human cancers inhibits cell growth and proliferation (91)(92)(93)(94). These results suggest a tumor suppressor function for HtrA proteinases.…”

Section: High-temperature Requirement Proteinasesmentioning

confidence: 88%

Emerging roles of serine proteinases in tissue turnover in arthritis

Milner

Patel

Rowan

2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…HtrA1 was originally identified as a gene down-regulated in SV40-transformed fibroblasts (Zumbrunn and Trueb, 1996). Further studies have revealed that HtrA1 is involved in cancer progression and chemotherapy-induced cytotoxicity (Chien et al, 2004(Chien et al, , 2006Bowden et al, 2006), in bone and cartilage development as well as arthritic disease (Tsuchiya et al, 2005;Grau et al, 2006) and in amyloid precursor protein processing (Grau et al, 2005). However, the highest level of HtrA1 expression was found in the human placenta, suggesting that HtrA1 may play important roles in placental formation and function (Nie et al, 2003a).…”

Section: Introductionmentioning

confidence: 99%

Distinct expression and localization of serine protease HtrA1 in human endometrium and first‐trimester placenta

Nie¹,

Hale²,

Liu³

et al. 2006

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternaltrophoblast interface suggests that HtrA1 may play a role in placental development. Developmental Dynamics 235:3448 -3455, 2006.

show abstract

Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer

Cited by 83 publications

References 31 publications

Expression of human HtrA1, HtrA2, HtrA3 and TGF-β1 genes in primary endometrial cancer

Expression of human HtrA1, HtrA2, HtrA3 and TGF-β1 genes in primary endometrial cancer

Emerging roles of serine proteinases in tissue turnover in arthritis

Distinct expression and localization of serine protease HtrA1 in human endometrium and first‐trimester placenta

Contact Info

Product

Resources

About