ArticleMolecular cancer2012
Nicotine, IFN-γ and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades.
Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.International journal of molecular sciences · 2024Article
- E2F1/2/4 mRNA is associated with immune infiltration and are potential biomarkers for the prognosis of human gastric carcinoma.Translational cancer research · 2021Article
- Role of the parasympathetic nervous system in cancer initiation and progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing.Frontiers in oncology · 2020Article
- Article
- Nicotinic acetylcholine receptors and cancer.Biomedical reports · 2016Article
- The canonical Wnt pathway regulates the metastasis-promoting mucin MUC4 in pancreatic ductal adenocarcinoma.Molecular oncology · 2016Article
- Article
- E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.Cell death and differentiation · 2015Article
- Mucolytic Agents Can Enhance HER2 Receptor Accessibility for [(89)Zr]Trastuzumab, Improving HER2 Imaging in a Mucin-Overexpressing Breast Cancer Xenograft Mouse Model.Molecular imaging and biology · 2015Article
- The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression.Cancers · 2015Review
- Riding the spermatogenic wave: profiling gene expression within neonatal germ and sertoli cells during a synchronized initial wave of spermatogenesis in mice.Biology of reproduction · 2014Article
- Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability.British journal of cancer · 2014Article
- Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in smokers.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Guggulsterone decreases proliferation and metastatic behavior of pancreatic cancer cells by modulating JAK/STAT and Src/FAK signaling.Cancer letters · 2013Article
- Activation of Akt pathway by transcription-independent mechanisms of retinoic acid promotes survival and invasion in lung cancer cells.Molecular cancer · 2013Article
- Nicotine and lung cancer.Journal of carcinogenesis · 2013Article
- Nicotine induces inhibitor of differentiation-1 in a Src-dependent pathway promoting metastasis and chemoresistance in pancreatic adenocarcinoma.Neoplasia (New York, N.Y.) · 2012Article
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5 authors at 3 institutions in 1 country.
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Abstract
backgroundThe membrane-bound mucins are thought to play an important biological role in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce the expression of MUC4 in pancreatic cancer cell lines CD18, CAPAN2, AsPC1 and BxPC3.
resultsChromatin immunoprecipitation assays and real-time PCR showed that transcription factors E2F1 and STAT1 can positively regulate MUC4 expression at the transcriptional level. IFN-γ and RA could collaborate with nicotine in elevating the expression of MUC4, utilizing E2F1 and STAT1 transcription factors. Depletion of STAT1 or E2F1 abrogated the induction of MUC4; nicotine-mediated induction of MUC4 appeared to require α7-nicotinic acetylcholine receptor subunit. Further, Src and ERK family kinases also mediated the induction of MUC4, since inhibiting these signaling molecules prevented the induction of MUC4. MUC4 was also found to be necessary for the nicotine-mediated invasion of pancreatic cancer cells, suggesting that induction of MUC4 by nicotine and other agents might contribute to the genesis and progression of pancreatic cancer.
conclusionsOur studies show that agents that can promote the growth and invasion of pancreatic cancer cells induce the MUC4 gene through multiple pathways and this induction requires the transcriptional activity of E2F1 and STAT1. Further, the Src as well as ERK signaling pathways appear to be involved in the induction of this gene. It appears that targeting these signaling pathways might inhibit the expression of MUC4 and prevent the proliferation and invasion of pancreatic cancer cells.
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