Regulation of breast cancer oncogenesis by the cell of origin's differentiation state.

Autor:	Petrova SC; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA.; These authors contributed equally to this work., Ahmad I; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA.; These authors contributed equally to this work., Nguyen C; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA., Ferrell SD Jr; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA., Wilhelm SR; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA., Ye Y; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA., Barsky SH; Cancer Center and Institute for Personalized Medicine, California University of Science and Medicine, Colton, CA 92324, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2020 Oct 27; Vol. 11 (43), pp. 3832-3848. Date of Electronic Publication: 2020 Oct 27 (Print Publication: 2020).
DOI:	10.18632/oncotarget.27783
Abstrakt:	Human breast cancer which affects 1/8 women is rare at a cellular level. Even in the setting of germline BRCA1/BRCA2, which is present in all breast cells, solitary cancers or cancers arising at only several foci occur. The overwhelming majority of breast cells (10 9 -10 12 cells) resist transformation. Our hypothesis to explain this rareness of transformation is that mammary oncogenesis is regulated by the cell of origin's critical window of differentiation so that target cells outside of this window cannot transform. Our novel hypothesis differs from both the multi-hit theory of carcinogenesis and the stem/progenitor cell compartmental theory of tumorigenesis and utilizes two well established murine transgenic models of breast oncogenesis, the FVB/N-Tg (MMTV-PyVT)634Mul/J and the FVB-Tg (MMTV-ErbB2) NK1Mul/J. Tail vein fibroblasts from each of these transgenics were used to generate iPSCs. When select clones were injected into cleared mammary fat pads, but not into non-orthotopic sites of background mice, they exhibited mammary ontogenesis and oncogenesis with the expression of their respective transgenes. iPSC clones, when differentiated along different non-mammary lineages in vitro , were also not able to exhibit either mammary ontogenesis or oncogenesis in vivo . Therefore, in vitro and in vivo regulation of differentiation is an important determinant of breast cancer oncogenesis. Competing Interests: CONFLICTS OF INTEREST The authors declare that they, at the present time, have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None of the sources of support listed influenced the collection, analysis and interpretation of data, the generation of the hypothesis, the writing of the manuscript or the decision to submit the manuscript for publication. (Copyright: © 2020 Petrova et al.)
Databáze:	MEDLINE
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