Abstract
Interleukin-17 (IL-17) has been shown to promote development of prostate, colon, skin, lung, breast, and pancreatic cancer. The purpose of this study was to determine if IL-17 regulates MTA1 expression and its biological consequences. Human cervical cancer HeLa and human prostate cancer DU-145 cell lines were used to test if IL-17 regulates metastasis associated 1 (MTA1) mRNA and protein expression using quantitative reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Cell migration and invasion were studied using wound healing assays and invasion chamber assays. Thirty-four human cervical tissues were stained for IL-17 and MTA1 using immunohistochemical staining. We found that IL-17 increased MTA1 mRNA and protein expression in both cell lines. Cell migration was accelerated by IL-17, which was abolished by knockdown of MTA1 expression with small interference RNA (siRNA). Further, cell invasion was enhanced by IL-17, which was eliminated by MTA1 knockdown. Human cervical intra-epithelial neoplasia (CIN) and cervical cancer tissues had increased number of IL-17-positive cells and MTA1 expression compared to normal cervical tissues. The number of IL-17-positive cells was positively correlated with MTA1 expression. These findings demonstrate that IL-17 upregulates MTA1 mRNA and protein expression to promote HeLa and DU-145 cell migration and invasion.
Highlights
Yao et al [1, 2] first identified interleukin-17 (IL-17, named IL-17A) and its first receptor IL-17 receptor A (IL-17RA) [3]
We previously found that metastasis associated 1 (MTA1) expression was decreased in Il17rc-null mouse prostate tumors compared to Il-17rc-expressing mouse prostate tumors [27]
After normalization based on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) levels, we found that IL17A significantly induced MTA1 protein expression at 36 h in both HeLa and DU-145 cells (Figures 1C,D)
Summary
Yao et al [1, 2] first identified interleukin-17 (IL-17, named IL-17A) and its first receptor IL-17 receptor A (IL-17RA) [3]. Reddi’s lab subcloned IL-17 receptor C (IL-17RC) [7]. Steiner et al [12] reported that IL-17A and IL-17RA expression is increased in prostate cancer and Drake’s lab found. IL-17 Upregulates MTA1 in Cancer increased TH17 cells in prostate cancer [13]. Gupta’s lab found IL-17-expressing macrophages and neutrophils in the lesions of proliferative inflammatory atrophy [14]—a precursor to prostatic intraepithelial neoplasia (PIN) and carcinoma [15]. Many independent research groups have shown that IL-17 promotes the development of colon [16,17,18,19], skin [20, 21], breast [22], lung [23, 24], and pancreatic cancer [25]. Our lab has demonstrated that IL-17 promotes development of hormonenaïve prostate cancer and castration-resistant prostate cancer (CRPC) [26, 27]
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