Expression profiles of p53, p21, bax and bcl-2 proteins in all-trans-retinoic acid treated primary and metastatic melanoma cells.
We have previously shown that all-trans-retinoic acid (atRA) induces apoptosis in melanoma cells and primary melanoma cells are more sensitive to the exposure of atRA than the matched metastases. However, mechanisms behind the atRA-induced apoptosis have not been studied. In this study, we used a similar cell culture model system of matched primary and metastatic melanoma cells from the same patient to investigate whether p53 and bcl-2 family proteins were involved in atRA-induced apoptosis. The primary and metastatic melanoma cells were exposed to 0.1 and 10 micro M atRA in serum-free RPMI 1640 cell culture medium in the dark for up to 96 h. The protein expression of p53, p21, bax and bcl-2 were examined by Western blotting and immunocytochemistry. Expression of p53, p21 and bax was increased, and bcl-2 was decreased in melanoma cells after exposure to atRA at different concentrations for various periods of time. The changes of p53, p21, bax, and bcl-2 protein levels were dose- and time-dependent. The primary melanoma cells were more sensitive to the atRA treatments than cells from matched metastatic melanoma. These data indicate that p53, p21, bax and bcl-2 proteins were involved in atRA-induced apoptosis in melanoma cells. Modification of these protein levels in the tumour cells might be beneficial for early treatment of melanoma.
Zhang
Hong
H
Division of Dermatology, Clinical Research Centre, Department of Biomedicine and Surgery, Linköping University, SE-581 85 Linköping, Sweden. hong.zhang@ibk.liu.se
Rosdahl
Inger
I
D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014212:Tretinoin