Loss of estrogen-responsiveness and impaired E-cadherin expression/function has been linked to increased metastatic potential of breast cancer cells. In this study, we report that proliferation of breast cancer cells can resume following removal of a toxic stimulus causing severe impairment of cell adhesion and estrogen responsiveness. This type of response was induced by okadaic acid (OA) in MCF-7 cells, and was accompanied by an almost complete block of DNA synthesis, loss of cell-cell contact and cell detachment from culture dishes, loss of estrogen receptor (ER), progesterone receptor (PR) and E-cadherin, whereas only a weak, if any, inhibition of protein synthesis could be observed. These responses were detected in MCF-7 cells after a 1-day treatment with 50 nM OA, and could be reversed if OA-treated cells were recovered in a culture medium devoid of the toxin, so that rescued cells resumed growth 8-12 days after replating. By pulse-chase experiments, we found that protein synthesis was not significantly affected in rescued cells, whose DNA synthesis, instead, was almost completely blocked during the first days of MCF-7 cell rescue from OA treatment. We also analyzed E-cadherin, mitogen activated protein kinase isoforms ERK1 and ERK2, Bcl-2 and BAX proteins during the rescue of MCF-7 cells from OA-induced cell death, and found that their expression followed temporally defined patterns. Cellular levels of E-cadherin returned to control levels within the first days of the rescue, followed by ER, ERK1, and ERK2, and finally by Bcl-2 and BAX proteins. Under our experimental conditions, restoration of cell adhesion did not require a functional ER system, but recovery of a normal ER pool accompanied resumption of estrogen-dependent proliferation of OA-treated MCF-7 cells.
Recovery of cellular E-cadherin precedes replenishment of estrogen receptor and estrogen-dependent proliferation of breast cancer cells rescued from a death stimulus / C., Malaguti; Rossini, Gian Paolo. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 192(2002), pp. 171-181.
Data di pubblicazione: | 2002 |
Titolo: | Recovery of cellular E-cadherin precedes replenishment of estrogen receptor and estrogen-dependent proliferation of breast cancer cells rescued from a death stimulus |
Autore/i: | C., Malaguti; Rossini, Gian Paolo |
Autore/i UNIMORE: | |
Rivista: | |
Volume: | 192 |
Pagina iniziale: | 171 |
Pagina finale: | 181 |
Codice identificativo ISI: | WOS:000176603000006 |
Codice identificativo Scopus: | 2-s2.0-0036301117 |
Codice identificativo Pubmed: | 12115723 |
Citazione: | Recovery of cellular E-cadherin precedes replenishment of estrogen receptor and estrogen-dependent proliferation of breast cancer cells rescued from a death stimulus / C., Malaguti; Rossini, Gian Paolo. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 192(2002), pp. 171-181. |
Tipologia | Articolo su rivista |
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