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Cancer Letters
Adan, Y., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Goldman, Y., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Haimovitz, R., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Mammon, K., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Eilon, T., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Tal, S., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Tene, A., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Karmel, Y., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Shinitzky, M., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Breast cancer cells in their virulent undifferentiated state are characterized by lack of functional estrogen receptors (ER) and/or progesterone receptors (PR) as well as relatively low levels of other normal differentiation markers such as milk proteins and lipid droplets. To date, no method for in situ elevation of the state of differentiation of breast cancer cells has yet been proven effective in patients. We have recently shown that 1,3 cyclic propanediol phosphate (1,3cPP), an analog of 1,3 cyclic glycerophosphate (1,3cGP), can promote morphological, neuronal-like differentiation in pheochromocytoma-12 cells in vitro. In view of this observation, we tested the potential of 1,3cPP to elevate the state of cellular differentiation of the human breast cancer cell lines MCF-7 (ER+) and HCC1954 (ER-), as characterized by the expression of steroid receptors, casein kinase, lipid droplet histology and signal-transduction gene profiles. In the range of 5-100 μM 1,3cPP the in vitro expression of ER-α, PR and casein kinase increased by approximately 2-fold while the mRNA transcription increased by 2-6-fold. Moreover, following 9-12 days of incubation with 1,3cPP, HCC1954 cells exhibited a significant increase in the production of lipid droplets as observed by Oil Red O staining. The in vivo effect of 1,3cPP on MCF-7 xenografted into nude mice was also determined. After 4 biweekly i.p. injections of 0.5 mg 1,3 cPP per mouse, tumors in the 1,3cPP treated virtually did not grow at all while the tumors in the control group grew rapidly. Based on these findings, we propose that this novel differentiating compound has the potential to transform the malignant tumor phenotype into a near-normal phenotype, as well as to sensitize the tumor cells to anti-estrogen therapy via upgrading the status of steroid hormone receptors. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
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תנאי שימוש
Phenotypic differentiation of human breast cancer cells by 1,3 cyclic propanediol phosphate
194
Adan, Y., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Goldman, Y., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Haimovitz, R., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Mammon, K., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Eilon, T., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Tal, S., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Tene, A., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Karmel, Y., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Shinitzky, M., Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Phenotypic differentiation of human breast cancer cells by 1,3 cyclic propanediol phosphate
Breast cancer cells in their virulent undifferentiated state are characterized by lack of functional estrogen receptors (ER) and/or progesterone receptors (PR) as well as relatively low levels of other normal differentiation markers such as milk proteins and lipid droplets. To date, no method for in situ elevation of the state of differentiation of breast cancer cells has yet been proven effective in patients. We have recently shown that 1,3 cyclic propanediol phosphate (1,3cPP), an analog of 1,3 cyclic glycerophosphate (1,3cGP), can promote morphological, neuronal-like differentiation in pheochromocytoma-12 cells in vitro. In view of this observation, we tested the potential of 1,3cPP to elevate the state of cellular differentiation of the human breast cancer cell lines MCF-7 (ER+) and HCC1954 (ER-), as characterized by the expression of steroid receptors, casein kinase, lipid droplet histology and signal-transduction gene profiles. In the range of 5-100 μM 1,3cPP the in vitro expression of ER-α, PR and casein kinase increased by approximately 2-fold while the mRNA transcription increased by 2-6-fold. Moreover, following 9-12 days of incubation with 1,3cPP, HCC1954 cells exhibited a significant increase in the production of lipid droplets as observed by Oil Red O staining. The in vivo effect of 1,3cPP on MCF-7 xenografted into nude mice was also determined. After 4 biweekly i.p. injections of 0.5 mg 1,3 cPP per mouse, tumors in the 1,3cPP treated virtually did not grow at all while the tumors in the control group grew rapidly. Based on these findings, we propose that this novel differentiating compound has the potential to transform the malignant tumor phenotype into a near-normal phenotype, as well as to sensitize the tumor cells to anti-estrogen therapy via upgrading the status of steroid hormone receptors. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
Scientific Publication
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