This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, K. Articles by Kim, S.-J. Search for Related Content PubMed PubMed Citation Articles by Park, K. Articles by Kim, S.-J.

The E1A Oncogene Induces Resistance to the Effects of 1,25-Dihydroxyvitamin D₃ on Inhibition of Growth of Mouse Keratinocytes

Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892 [K.P., H.B., A.H., A.B.R., M.B.S., S-J.K.], and Cutaneous Cancer Center, Massachusetts General Hospital, MGH East, Building 149, Charlestown, Massachusetts 02129-2060 [G. P. D.]

1,25-Dihydroxyvitamin D₃ [1,25-(OH)₂D₃] inhibited DNA synthesis in transformed mouse keratinocytes (Pam212) in a time- and dose-dependent manner as measured by [³H]thymidine incorporation. To investigate the mechanism through which 1,25-(OH)₂D₃ acts, we examined its effects on Pam212 cells further transformed with the E1A oncogene. Here, we show that transformation of the cells with the E1A oncogene induced resistance to the effects of 1,25-(OH)₂D₃ on inhibition of growth of Pam212 cells. While 1,25-(OH)₂D₃ treatment increased the level of expression of vitamin D receptor mRNA 20-fold in parental cells, the E1A-transformed cells failed to express vitamin D receptor mRNA even after treatment with 1,25-(OH)₂D₃. Transfection of the E1A-transformed cell line with an expression construct encoding the vitamin D receptor restored receptor expression as well as the inhibition of growth by 1,25-(OH)₂D₃. These results suggest that one of the mechanisms for acquisition of 1,25-(OH)₂D₃ resistance induced by E1A may involve loss of vitamin D receptor inducibility by 1,25-(OH)₂D₃.

¹ Present address: Division of Hemato-Oncology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University, 445 Kil-Dong, Kangdong-Gu, Seoul, 134-010, Korea.

² To whom requests for reprints should be addressed, at Building 41, Room B1106, NIH, National Cancer Institute, Bethesda, MD 20892.

Received 9/ 6/94. Accepted 10/20/94.

This article has been cited by other articles:

				X. Qi, R. Pramanik, J. Wang, R. M. Schultz, R. K. Maitra, J. Han, H. F. DeLuca, and G. Chen The p38 and JNK Pathways Cooperate to trans-Activate Vitamin D Receptor via c-Jun/AP-1 and Sensitize Human Breast Cancer Cells to Vitamin D3-induced Growth Inhibition J. Biol. Chem., July 12, 2002; 277(29): 25884 - 25892. [Abstract] [Full Text] [PDF]

				C. Agarwal, A. Lambert, R. A.S. Chandraratna, E. A. Rorke, and R. L. Eckert Vitamin D Regulates Human Ectocervical Epithelial Cell Proliferation and Insulin-Like Growth Factor-Binding Protein-3 Level Biol Reprod, March 1, 1999; 60(3): 567 - 572. [Abstract] [Full Text]

				D. H. Kim, J. H. Chang, K. H. Lee, H.-Y. Lee, and S.-J. Kim Mechanism of E1A-Induced Transforming Growth Factor-beta (TGF-beta ) Resistance in Mouse Keratinocytes Involves Repression of TGF-beta Type II Receptor Transcription J. Biol. Chem., January 3, 1997; 272(1): 688 - 694. [Abstract] [Full Text] [PDF]