Access Type
Open Access Embargo
Date of Award
January 2022
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Pharmaceutical Sciences
First Advisor
Fei Chen
Abstract
Arsenic (As3+), a metalloid abundant in the environment, is classified as a group I carcinogen associated with several common human cancers, including cancers in the lung, skin, bladder, liver, and prostate (Wei, Zhang & Tao, 2019b). The mechanisms of As3+-induced carcinogenesis had been extensively studied, and different mechanisms might be involved in various types of cancer (Wei, Zhang & Tao, 2019b). Recent studies showed that exposure to a high dose of arsenic is able to induce lung cancer. Moreover, arsenic activates oncogenic signaling pathways such as MAPKs, EGFR/RAS/RAF, PI3K/AKT, and JNK/STAT3 pathways as well as epigenetic alterations such as miRNAs expression to regulate the carcinogenesis. Meanwhile, prolonged exposure to a low concentration of arsenic can increase the risk of lung cancer also (Fernández, López, Vivaldi & Coz, 2012; Liao et al., 2009). Emerging evidence indicated that prolonged exposure to arsenic promotes malignant transformation and induces normal cells to have cancer-stem-like properties (Ngalame, Tokar, Person & Waalkes, 2014). In the present report, we revealed that exposure to As3+ for a short time period inhibited tyrosine-705 phosphorylation of signal transducer and activator of transcription 3 (pSTAT3Y705) and induced Src homology region 2 domain-containing phosphatase-1 (SHP-1). In addition, we found that long-term exposure of the cells to As3+ activates phosphorylation of STAT3 at serine 727 (pSTAT3S727) as well as pSTAT3Y705. Moreover, As3+ is able to induce the expression of miRNA-21 (miR-21) and decrease the expression of PDCD4. Taken together, our data suggest that activation of STAT3 and induction of miR-21 are responsible for the reduced expression of PDCD4, which may play a significant role in the As3+-induced transformation of BEAS-2B cells.
Recommended Citation
Almutairy, Bandar, "The Effect Of Acute And Chronic Arsenic Exposure On Malignant Transformation Of The Human Bronchial Epithelial Cell (beas-2b)" (2022). Wayne State University Dissertations. 3588.
https://digitalcommons.wayne.edu/oa_dissertations/3588