Sensitivity to cis-diamminedichloroplatinum in human cancer cells is related to expression of cyclin D1 but not C-RAF-1 protein
✍ Scribed by Hilmar M. Warenius; Laurence A. Seabra; Paula Maw
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 778 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Although several oncogenes, including c-myc, ras and c-raf-I, have been implicated in cellular resistance to ionising radiation, there is less information relating oncogene expression to cisdiamminedochloroplatinum (CDDP) resistance. However, transfection of c-myc or v-H-ras and activation of protein kinase C (PKC), which contributes to the RAF-I, MAP kinase signal transduction pathway, can influence therapeutic response to CDDP. Activation of PKC increases CDDP sensitivity, whilst transfected c-myc or v-H-ras induce CDDP resistance. We have previously reported that human in vitro cell lines show different patterns of sensitivity to CDDP and 4 MeV X-irradiation. In these cells radiation sensitivity is related to high levels of expression of the c-raf-I proto-oncogene. We thus predicted that cells sensitive to CDDP might show a different relationship to c-raf-I expression. In addition, because cyclin DI expression can be upregulated by the myc or ras oncogenes, we also chose to study putative relationships between cyclin D I protein levels and intrinsic cellular sensitivity to CDDP and y-irradiation. We report that in the 16 human cell lines which we have studied, high cyclin DI expression is related to CDDP resistance but has no relationship with radiation responsiveness, whereas high c-raf-I expression, although related to radiosensitivity has no relationship with CDDP responsiveness.