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Journal of Environmental Pathology, Toxicology and Oncology
Impact-faktor: 1.241 5-jähriger Impact-Faktor: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Druckformat: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2018026684
pages 69-81

PI3K/Akt Pathway and miR-21 are Involved in N-Ethyl-N-Nitrosourea-Induced F1 Mouse Lung Tumorigenesis: Effect of Inositol Hexaphosphate

Satya Sahay
Environmental Carcinogenesis Laboratory Council of Scientific and Industrial Research (CSIR)–Indian Institute of Toxicology Research (IITR), Mahatma Gandhi Marg, Lucknow 226001, India
Prakash Tiwari
Environmental Carcinogenesis Laboratory Council of Scientific and Industrial Research (CSIR)–Indian Institute of Toxicology Research (IITR), Mahatma Gandhi Marg, Lucknow 226001, India
Manuraj Pandey
Environmental Carcinogenesis Laboratory Council of Scientific and Industrial Research (CSIR)–Indian Institute of Toxicology Research (IITR), Mahatma Gandhi Marg, Lucknow 226001, India
Krishna P. Gupta
Environmental Carcinogenesis Laboratory Council of Scientific and Industrial Research (CSIR)–Indian Institute of Toxicology Research (IITR), Mahatma Gandhi Marg, Lucknow 226001, India

ABSTRAKT

The risk of cancer development in offspring due to carcinogen exposure during pregnancy is a serious issue. In this study, we explored the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and microRNA-21 (miR-21) in transplacental lung tumorigenesis and its prevention by dietary compound inositol hexaphosphate (IP6) in F1 mice. Balb/c mice were exposed to the N-ethyl-N-nitrosourea (ENU) intraperitoneally on the 17th day of gestation. After weaning, half of the litters were fed with oral 2% IP6. At the end of 30, 120, or 240 days, we did not observe any effect on fetal viability or weight between ENU-exposed and non-exposed litters and the same was true of IP6. Altered expressions of the PI3K/Akt pathway were observed in F1 mice. Further, miR-21 expressions were found to be modulated at the respective time as well, along with the activation of matrix metalloproteinase (MMP-9) and vascular endothelial growth factor expression. Akt activation also enhanced the expression of cyclin D1, cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κBp50), and mammalian target of rapamycin (mTOR). IP6-fed F1 mice showed reduced tumorigenesis along with reduced expression of the PI3K/Akt pathway miR-21 and downstream targets. The PI3K/Akt pathway and miR-21 are involved in transplacental lung tumorigenesis, whereas IP6 seemed to affect lung tumorigenesis by suppressing the expression of the PI3K/Akt pathway in F1 mice.


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