Transformation-selective apoptotic program triggered by farnesyltransferase inhibitors requires Bin1

Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts

“…Previous work showed that as in the case of TR MEFs Bin1 loss does not promote tumor formation by ER MEFs. 15 We observed that Bin1 deletion in these cells ablated sensitivity to TNF-induced apoptosis (Fig. 5A).…”

“…Bin1 loss did not benefit tumor formation by TR MEFs (this study) or ER MEFs. 15 Thus, it is evident that Bin1 has a selective effect in the context of oncogenic transformation mediated by c-myc that is not shared with the viral oncoproteins, despite their parallel roles in cell transformation. Such .…”

“…MEFs transformed by the adenovirus E1A region (encoding the 9S, 12S, and 13S E1A oncoproteins) plus activated H-RasV12, referred to as ER MEFs or ER cells, have been described previously. 15 For retroviral gene transduction, the plasmid vector MSCV-pac 33 was modified to express human c-Myc, H-RasV12, or Bin1 [-10] or Bin1[-10-13] cDNAs 30,34 via the production of helper-free viruses. To generate retroviruses, 293 cell-derived Phoenix cells 35 plated the previous day at 2 x 10 6 per 10 cm dish were transfected transiently with plasmids mixed with Lipofectamine 2000 as recommended by the vendor (Invitrogen).…”

“…Therefore, to examine this question we used MEFs transformed by the adenovirus E1A early region plus activated H-ras (termed ER MEFs or ER cells) that had been generated for another study. 15 The relevance of this system is justified by functional similarity between c-myc and E1A in murine cell transformation, 48 the requirement of c-myc for E1A to drive cell proliferation, 42 and the well-documented ability of the E1A early region to sensitize murine fibroblasts to TNF-induced apoptosis (e.g., ref. 49).…”

“…Notably, the benefit of Bin1 loss to cell growth and survival appears to be contingent on cell transformation. [13][14][15][16] Taken together, these studies suggest that Bin1 may restrain cellular proliferation and survival in a contextual manner that is dependent on some feature of neoplastic pathophysiology.…”