Endoplasmic reticulum stress is activated in endometrial adenocarcinoma

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• 作者：Giuseppe Bifulco^a ; ^{giuseppe.bifulco@unina.it} ; Claudia Miele^b ; Bruno Di Jeso^c ; Francesco Beguinot^b ; Carmine Nappi^a ; Costantino Di Carlo^a ; Silvana Capuozzo^d ; Giuseppe Terrazzano^e ; Luigi Insabato^d ; Luca Ulianich^b
• 关键词：Endoplasmic reticulum ; Stress ; Endometrial cancer
• 刊名：Gynecologic Oncology
• 出版年：2012
• 期刊代码：295_00908258
• 类别：med
• 出版时间：April, 2012
• 卷：125
• 期：1
• 页码：220-225
• 文件大小：921 K

摘要

Objectives

Endometrial cancer is the most common malignancy of the female genital tract. However, in spite of a huge advance in our understanding of endometrial cancer biology, therapeutic modalities haven't significantly changed over the past 40 years. The activation of the Unfolded Protein Response (UPR) and GRP78 increase following Endoplasmic Reticulum (ER) stress have been recently identified as mechanisms favoring growth, invasion and resistance to therapy of different types of cancer. However, a possible role of ER stress and GRP78 in endometrial cancer has never been investigated.

Methods

Tissue specimens from normal and neoplastic endometrium were analyzed for the expression of the ER stress markers GRP78, ATF6 and CHOP by Real-Time RT-PCR. In addition, GRP78 protein expression and localization were evaluated by Western blot and immunohistochemistry, respectively. The effect of GRP78 knock down on cell growth of Ishikawa cells was analyzed by proliferation curve analysis.

Results

In this analysis, the expression levels of GRP78, ATF6 and CHOP mRNAs were significantly increased in specimens of endometrioid endometrial carcinomas. GRP78 and ATF6 protein expression levels were also increased in specimens of endometrial adenocarcinomas. GRP78 knock down caused a decrease of Ishikawa cells' growth.

Conclusions

The increased expression of ER stress markers in endometrioid endometrial carcinomas suggests a role for ER stress, the UPR and, possibly, GRP78 in endometrial cancer. Whether these mechanisms have a substantial function in the pathogenesis of malignant transformation of human endometrium is still under investigation in our laboratory.