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 Radinsky, R. Articles by Fidler, I. J. Search for Related Content PubMed PubMed Citation Articles by Radinsky, R. Articles by Fidler, I. J.

Transcriptional Induction of the Melanocyte-stimulating Hormone Receptor in Brain Metastases of Murine K-1735 Melanoma¹

Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [R. R., P. J. B., R. T., R. Z., I. J. F.], and Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, Oregon 97201 [R. D. C.]

Metastatic K-1735 murine melanoma cells are amelanotic in culture or in the subcutis of syngeneic mice. When injected into the internal carotid artery, these cells produce melanotic brain metastases. The production of melanin in tumor cells growing in the brain was directly correlated with induction of melanocyte-stimulating hormone receptor (MSH-R) steadystate mRNA transcripts. K-1735 cells isolated from brain lesions and implanted into the subcutis or grown in culture lose MSH-R transcripts and become amelanotic. In contrast to K-1735 cells, B16-BL6 melanoma cells constitutively produce melanin and express high levels of MSH-R mRNA regardless of the site of growth. Somatic cell hybrids between K-1735 and B16 cells produced melanin and expressed high levels of MSH-R mRNA transcripts, regardless of the site of growth, suggesting the dominance of the B16 phenotype. Treatment with -MSH failed to upregulate MSH-R expression in cultured K-1735 cells or to maintain MSH-R expression in K-1735 cells isolated from brain metastases to be grown in culture. Responsiveness to -MSH as determined by cell proliferation, melanin production, and intracellular accumulation of cyclic AMP directly correlated with MSH-R expression. These data demonstrate that a specific organ environment influences the phenotype of metastatic cells by regulation of specific genes that encode for cell surface receptors.

¹ Supported in part by Cancer Center Support Core Grants CA 16672 and R35-CA 42107 (to I. J. F.) from the National Cancer Institute, National Institutes of Health, Grant PF-3446 from the American Cancer Society (to R. R.), and Grant AR 42415 from the National Institutes of Health (to R. D. C.).

² To whom requests for reprints should be addressed, at the Department of Cell Biology, Box 173, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 7/25/94. Accepted 11/ 1/94.

This article has been cited by other articles:

				S. Kim, Y.-W. Park, B. A. Schiff, D. D. Doan, Y. Yazici, S. A. Jasser, M. Younes, M. Mandal, B. N. Bekele, and J. N. Myers An Orthotopic Model of Anaplastic Thyroid Carcinoma in Athymic Nude Mice Clin. Cancer Res., March 1, 2005; 11(5): 1713 - 1721. [Abstract] [Full Text] [PDF]

				C. Parker, B. J. Roseman, C. D. Bucana, R. Tsan, and R. Radinsky Preferential Activation of the Epidermal Growth Factor Receptor in Human Colon Carcinoma Liver Metastases in Nude Mice J. Histochem. Cytochem., May 1, 1998; 46(5): 595 - 602. [Abstract] [Full Text]