Expression profiles of Id1 and p16 proteins in all-trans-retinoic acid-induced apoptosis and cell cycle re-distribution in melanoma.
All-trans-retinoic acid (atRA) exerts its effects via apoptosis and cell cycle re-distribution. However, the mechanisms behind the effects have not been fully understood. In this study, we used a model system of matched primary and metastatic melanoma cells to investigate whether expression of Id1 and p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution. Melanoma cells were exposed to 0.1 or 10 microM atRA for 1-96 h. Apoptosis and cell cycle were measured by flow cytometry. Expression of Id1 and p16 proteins was examined by Western blotting and immunocytochemistry. After exposure to atRA we found a marked increase in apoptosis and cell cycle re-distribution in both primary and metastatic melanoma cells. Expression level of Id1 protein was decreased and the p16 was increased in a dose- and time-dependent (P<0.05) manner after treatment with atRA. Alterations of these proteins were more pronounced in the primary melanoma cells than the matched metastases (P<0.05). These data suggested that the alterations of Id1 and/or p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution in melanoma. These expression profiles of Id1 and p16 proteins may provide molecular evidence for better chemotherapy primarily for early stages 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
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051798:Inhibitor of Differentiation Protein 1; D008545:Melanoma / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects; D012097:Repressor Proteins / Q000096:biosynthesis / Q000187:drug effects*; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014212:Tretinoin