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10.1038/s41389-018-0053-7

http://scihub22266oqcxt.onion/10.1038/s41389-018-0053-7
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C5968032!5968032!29795364
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suck abstract from ncbi


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pmid29795364      Oncogenesis 2018 ; 7 (5): ä
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  • AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment #MMPMID29795364
  • Kalra R; Bhagyaraj E; Tiwari D; Nanduri R; Chacko AP; Jain M; Mahajan S; Khatri N; Gupta P
  • Oncogenesis 2018[May]; 7 (5): ä PMID29795364show ga
  • Early stage prostate cancers are dependent on androgens for their growth and survival and androgen withdrawal causes them to regress. Progressive prostate cancers eventually acquire androgen independence rendering anti-androgen therapy ineffective. However, the factors leading to this have not been adequately addressed. This study shows that AIRE finds differential expression in androgen-dependent and -independent prostate cancer cells. AIRE expression is more in androgen-independent cells due to its regulation by transcription factor Elk-1. These enhanced levels of AIRE modulate the prostate tumor microenvironment by transcriptionally activating a malignancy gene IL-6 in androgen-independent cells. Additionally, AIRE prevents the cancer cells from anticancer drug-induced death and enhances their invasiveness. Moreover, AIRE by modulating the cytokine milieu skews the tumor-associated macrophage polarization towards M2 phenotype with increased CD206 and CD163 expression. Subcutaneous mouse model of prostate cancer revealed AIRE+/+ mice forming a palpable tumor and presents lymphadenopathy however, only a small benign tumor is observed in AIRE?/? mice and lymph nodes appear normal in size. In conclusion, our findings suggest AIRE as a probable factor in promoting prostate cancer progression.
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