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Apoptotic Conversion

Evidence for Exchange of Genetic Information between Prostate Cancer Cells Mediated by Apoptosis¹

Departments of Urology [A. d. l. T., M. W. C., M. B., R. B.] and Pathology [A. d. l. T., R. B.], The College of Physicians and Surgeons of Columbia University, New York, New York 10032, and Department of Urology, Henri Mondor Hospital, 94010 Créteil, France [A. d. l. T., D. K. C.]

Changes in the outer membrane of apoptotic cells can induce neighboring cells to become phagocytic. Using genetically marked prostate cancer cell lines, we explored the possibility that genetic information might be transferred from an apoptotic cell to a phagocytic neighbor. Neomycin-resistant LNCaP cells that overexpress bcl-2 (LNCaP^bcl-2/neo-r) were cocultured with hygromycin-resistant LNCaP cells (LNCaP^hygr-r). The cocultures were then transiently exposed to serum starvation to induce apoptosis of LNCaP^hygr-r cells. Surviving cells were then coselected in medium containing both antibiotics. Whereas monocultures of LNCaP^bcl-2/neo-r or LNCaP^hygr-r treated this way yielded no colonies, cocultures yielded dual-antibiotic-resistant clones at a frequency of approximately 1 in 10⁵. Pre-exposure to an apoptotic agent was required; cocultures not exposed to serum starvation yielded no dual-selectable colonies. Analysis of DNA extracted from a dual-resistant clone demonstrated that the restriction endonuclease pattern of the neo-r gene was unaltered when compared with the parental LNCaP^bcl-2/neo-r. However the hygr-r gene demonstrated an altered restriction endonuclease pattern in the dual-resistant derivative compared with the parental LNCaP^hygr-r cell line. This is evidence that genetic information can be transferred from one prostate cancer cell to another through the process of apoptosis, and we term this form of genetic transfer "apoptotic conversion."

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