PMC:5608921 / 22796-24631 JSONTXT

{"project":"2_test","denotations":[{"id":"28846079-24196716-79081953","span":{"begin":132,"end":134},"obj":"24196716"},{"id":"28846079-19571878-79081954","span":{"begin":431,"end":433},"obj":"19571878"},{"id":"28846079-21866153-79081955","span":{"begin":435,"end":437},"obj":"21866153"},{"id":"28846079-22143790-79081956","span":{"begin":439,"end":441},"obj":"22143790"},{"id":"28846079-12525422-79081957","span":{"begin":1229,"end":1231},"obj":"12525422"},{"id":"28846079-22870269-79081958","span":{"begin":1631,"end":1633},"obj":"22870269"}],"text":"Mechanisms of regeneration in carcinogenesis\nPostmitotic cells can contribute to tissue repair by dedifferentiation into stem cells.41 Our data support that the increased growth induced by HPV oncogenes at the initial stages of carcinogenesis is mostly due to the cell cycle re-entry of suprabasal cells without requiring dedifferentiation into basal-like cells (Figure 7) similar to what has been observed in regenerating tissues.42, 43, 44 Nonetheless, the re-entry into the cell cycle of postmitotic cells could be essential for dedifferentiation at later stages of carcinogenesis. Actually, this phenomenon might explain the increase in basal dividing cells in the epidermis of Tg(K10-E6/E7) mice as referred above. We propose that the long-term cooperation between E6/E7 and estradiol in cervical–uterine cancer development could result from the cumulative increase in new proliferating cells contributing to epithelial growth and carcinogenesis (Figure 7). In this regard, it was interesting to find an increased number of koilocyte-like and bi-nucleated cells in the chronically growing cervical epithelium of E2-treated Tg(K6b-E6/E7) mice, as occurs at the early stages of carcinogenesis in the HPV-infected human tissue.22\nCancer and regeneration are closely related processes. The present work supports this relationship showing that two well-known promoters of cancer, estradiol and HPV oncogenes, also promote regeneration. Furthermore, it is interesting the parallel estradiol-E6/E7 cooperation for growth observed between cervix and skin. Accordingly, as in the cervix, ERα has been implicated in skin carcinogenesis.45 Since ear regeneration is a simple experimental model, the data presented encourage further studies in regenerating ears of Tg(K6b-E6/E7) mice to understand the early stages in cervical carcinogenesis."}