کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525308 1546661 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleInduction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleInduction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis
چکیده انگلیسی


- This is the first study to demonstrate the role of placental specific 8 (Plac8) in Cd-induced prostate carcinogenesis.
- Silencing Plac8 expression suppress Cd-transformed prostate epithelial cell growth.
- Over expression of Plac8 in normal prostate epithelial cells causes resistance to Cd toxicity.

Chronic exposure to cadmium is known to be a risk factor for human prostate cancer. Despite over-whelming evidence of cadmium causing carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal-induced cellular transformation remain unclear. Acute exposure (up to 72 h) to cadmium induces apoptosis in normal prostate epithelial cells (RWPE-1), while chronic exposure (>1 year) transforms these cells to a malignant phenotype (cadmium-transformed prostate epithelial cells; CTPE). Increased expression of autophagy-regulated genes; Plac8, LC3B and Lamp-1; in CTPE cells was associated with cadmium-induced transformation. Increased expression of Plac8, a regulator of autophagosome/autolysosome fusion, facilitates the pro-survival function of autophagy and upregulation of pAKT(ser473) and NF-κβ, to allow CTPE to proliferate. Likewise, inhibition of Plac8 suppresses CTPE cell growth. Additionally, overexpression of Plac8 in RWPE-1 cells induces resistance to cadmium toxicity. Pharmacological inhibitors and an inducer of autophagy failed to affect Plac8 expression and CTPE cell viability, suggesting a unique role for Plac8 in cadmium-induced prostate epithelial cell transformation. These results support a role for Plac8 as an essential component in the cadmium-induced transformation of normal prostate epithelial cells to a cancerous state.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 408, 1 November 2017, Pages 121-129
نویسندگان
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