Human papillomavirus type 16 E7 oncoprotein upregulates the retinoic acid receptor-beta expression in cervical cancer cell lines and K14E7 transgenic mice

2015 ◽  
Vol 408 (1-2) ◽  
pp. 261-272 ◽  
Author(s):  
Jorge Gutiérrez ◽  
Enrique García-Villa ◽  
Rodolfo Ocadiz-Delgado ◽  
Enoc M. Cortés-Malagón ◽  
Juan Vázquez ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Retinoic Acid ◽  
Human Papillomavirus ◽  
Transgenic Mice ◽  
Cell Lines ◽  
Cancer Cell ◽  
Retinoic Acid Receptor ◽  
Human Papillomavirus Type 16 ◽  
Retinoic Acid Receptor Beta ◽  
Receptor Beta

scholarly journals Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5'-noncoding region.

1994 ◽  
Vol 127 (4) ◽  
pp. 1111-1119 ◽  
Author(s):  
A Zimmer ◽  
A M Zimmer ◽  
K Reynolds
Keyword(s):  
Retinoic Acid ◽  
Transgenic Mice ◽  
Retinoic Acid Receptor ◽  
Open Reading Frames ◽  
Wild Type ◽  
Retinoic Acid Receptor Beta ◽  
Eukaryotic Mrnas ◽  
Beta 2 ◽  
Reading Frames ◽  
Receptor Beta

The 40-S subunit of eukaryotic ribosomes binds to the capped 5'-end of mRNA and scans for the first AUG in a favorable sequence context to initiate translation. Most eukaryotic mRNAs therefore have a short 5'-untranslated region (5'-UTR) and no AUGs upstream of the translational start site; features that seem to assure efficient translation. However, approximately 5-10% of all eukaryotic mRNAs, particularly those encoding for regulatory proteins, have complex leader sequences that seem to compromise translational initiation. The retinoic-acid-receptor-beta 2 (RAR beta 2) mRNA is such a transcript with a long (461 nucleotides) 5'-UTR that contains five, partially overlapping, upstream open reading frames (uORFs) that precede the major ORF. We have begun to investigate the function of this complex 5'-UTR in transgenic mice, by introducing mutations in the start/stop codons of the uORFs in RAR beta 2-lacZ reporter constructs. When we compared the expression patterns of mutant and wild-type constructs we found that these mutations affected expression of the downstream RAR beta 2-ORF, resulting in an altered regulation of RAR beta 2-lacZ expression in heart and brain. Other tissues were unaffected. RNA analysis of adult tissues demonstrated that the uORFs act at the level of translation; adult brains and hearts of transgenic mice carrying a construct with either the wild-type or a mutant UTR, had the same levels of mRNA, but only the mutant produced protein. Our study outlines an unexpected role for uORFs: control of tissue-specific and developmentally regulated gene expression.

scholarly journals Retinoic acid receptor beta promoter methylation and risk of cervical cancer

2018 ◽  
Vol 7 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Chaninya Wongwarangkana ◽  
Nasamon Wanlapakorn ◽  
Jira Chansaenroj ◽  
Yong Poovorawan
Keyword(s):  
Cervical Cancer ◽  
Retinoic Acid ◽  
Promoter Methylation ◽  
Retinoic Acid Receptor ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Beta ◽  
Receptor Beta

scholarly journals Novel Clofarabine-Based Combinations with Polyphenols Epigenetically Reactivate Retinoic Acid Receptor Beta, Inhibit Cell Growth, and Induce Apoptosis of Breast Cancer Cells

2018 ◽  
Vol 19 (12) ◽  
pp. 3970 ◽  
Author(s):  
Katarzyna Lubecka ◽  
Agnieszka Kaufman-Szymczyk ◽  
Barbara Cebula-Obrzut ◽  
Piotr Smolewski ◽  
Janusz Szemraj ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Retinoic Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptor Beta ◽  
Receptor Beta

An epigenetic component, especially aberrant DNA methylation pattern, has been shown to be frequently involved in sporadic breast cancer development. A growing body of literature demonstrates that combination of agents, i.e. nucleoside analogues with dietary phytochemicals, may provide enhanced therapeutic effects in epigenetic reprogramming of cancer cells. Clofarabine (2-chloro-2′-fluoro-2′-deoxyarabinosyladenine, ClF), a second-generation 2′-deoxyadenosine analogue, has numerous anti-cancer effects, including potential capacity to regulate epigenetic processes. Our present study is the first to investigate the combinatorial effects of ClF (used at IC50 concentration) with epigallocatechin-3-gallate (EGCG, tea catechin) or genistein (soy phytoestrogen), at physiological concentrations, on breast cancer cell growth, apoptosis, and epigenetic regulation of retinoic acid receptor beta (RARB) transcriptional activity. In MCF7 and MDA-MB-231 cells, RARB promoter methylation and expression of RARB, modifiers of DNA methylation reaction (DNMT1, CDKN1A, TP53), and potential regulator of RARB transcription, PTEN, were estimated using methylation-sensitive restriction analysis (MSRA) and quantitative real-time polymerase chain reaction (qPCR), respectively. The combinatorial exposures synergistically or additively inhibited the growth and induced apoptosis of breast cancer cells, followed by RARB hypomethylation with concomitant multiple increase in RARB, PTEN, and CDKN1A transcript levels. Taken together, our results demonstrate the ability of ClF-based combinations with polyphenols to promote cancer cell death and reactivate DNA methylation-silenced tumor suppressor genes in breast cancer cells with different invasive potential.

scholarly journals Arg269 and Lys220 of retinoic acid receptor-beta are important for the binding of retinoic acid.

1994 ◽  
Vol 269 (30) ◽  
pp. 19516-19522
Author(s):  
N. Tairis ◽  
J.L. Gabriel ◽  
M. Gyda ◽  
K.J. Soprano ◽  
D.R. Soprano
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Beta ◽  
Receptor Beta

Sensitization of cervical cancer cell lines to low-dose radiation by retinoic acid does not require functional p53

2005 ◽  
Vol 97 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Todd D. Tillmanns ◽  
Scott A. Kamelle ◽  
Suresh Guruswamy ◽  
Natalie S. Gould ◽  
Teresa L. Rutledge ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Low Dose ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cell ◽  
Low Dose Radiation ◽  
Dose Radiation

scholarly journals The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Transgenic Mice ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Precancerous Lesions ◽  
Cancer Cell Lines ◽  
Cervical Carcinogenesis ◽  
Cervical Precancerous Lesions

AbstractIntegration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

scholarly journals Enhancer-promoter Activity of Human Papillomavirus Type 16 Long Control Regions Isolated from Cell Lines SiHa and CaSki and Cervical Cancer Biopsies

2000 ◽  
Vol 91 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Takuyo Kozuka ◽  
Yukimasa Aoki ◽  
Keiichi Nakagawa ◽  
Kuni Ohtomo ◽  
Hiroyuki Yoshikawa ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cell Lines ◽  
Promoter Activity ◽  
Human Papillomavirus Type 16 ◽  
Control Regions
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