HPV positive neuroendocrine cervical cancer cells are dependent on Myc but not E6/E7 viral oncogenes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Hang Yuan, Ewa Krawczyk, Jan Blancato, Christopher Albanese, Dan Zhou, Naidong Wang, Siddartha Paul, Faris Alkhilaiwi, Nancy Palechor-Ceron, Aleksandra Dakic, Shuang Fang, Sujata Choudhary, Tung-Wei Hou, Yun-Ling Zheng, Bassem R Haddad, Yukari Usuda, Dan Hartmann, David Symer, Maura Gillison, Seema Agarwal, Danny Wangsa, Thomas Ried, Xuefeng Liu, Richard Schlegel

ABSTRACT

Using conditional cell reprogramming, we generated a stable cell culture of an extremely rare and aggressive neuroendocrine cervical cancer. The cultured cells contained HPV-16, formed colonies in soft agar and rapidly produced tumors in immunodeficient mice. The HPV-16 genome was integrated adjacent to the Myc gene, both of which were amplified 40-fold. Analysis of RNA transcripts detected fusion of the HPV/Myc genes, arising from apparent microhomologous recombination. Spectral karyotyping (SKY) and fluorescent-in-situ hybridization (FISH) demonstrated coordinate localization and translocation of the amplified Myc and HPV genes on chromosomes 8 and 21. Similar to the primary tumor, tumor cell cultures expressed very high levels of the Myc protein and, in contrast to all other HPV-positive cervical cancer cell lines, they harbored a gain-of-function mutation in p53 (R273C). Unexpectedly, viral oncogene knockdown had no effect on the growth of the cells, but it did inhibit the proliferation of a conventional HPV-16 positive cervical cancer cell line. Knockdown of Myc, but not the mutant p53, significantly inhibited tumor cell proliferation. On the basis of these data, we propose that the primary driver of transformation in this aggressive cervical cancer is not HPV oncogene expression but rather the overexpression of Myc. More... »

PAGES

45617

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep45617

DOI

http://dx.doi.org/10.1038/srep45617

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084514006

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28378747


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