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Regulatory Controls of Oncotrophoblast Proteins and Developmental Alkaline Phosphatases in Cancer Cells¹

Tufts Cancer Research Center, Tufts University School of Medicine, Boston, Massachusetts 02111 [W. H. F.], and Department of Anatomy, Fairleith Dickinson University School of Denistry, Hackensack, New Jersey 07601 [R. N. S.]

The two oncotrophoblast proteins, Regan isoenzyme (placental-type alkaline phosphatase) and human chorionic gonadotrophin, are readily studied oncodevelopmental gene products in human cancer patients and in three experimental model systems. The latter consists of (a) HeLa sublines TCRC-1 and TCRC-2, which produce Regan and non-Regan isoenzymes, (b) HEp-2 and FL amnion cell lines as models for the reciprocal expression of developmental genes, and (c) modulation in vivo of developmental gene expression in HeLa cells. In the case of the third model, for example, HeLa TCRC-1 cells grow in immunosuppressed rats to form a tumor nodule, which expresses a new oncoamnion (FL) isoenzyme, while the Regan isoenzyme disappears. Return of the tumor cells to cell culture medium results in a disappearance of the oncoamnion (FL) species and the reappearance of Regan isoenzyme. This interesting model is expected to bridge the interpretation of experiments done in cell culture with observations made on tumors of cancer patients. Most helpful in interpretation of all these studies has been a chronology of early development. It appears that the counterparts of a number of tumor proteins appear as early as gametogenesis and as late as 10 weeks of gestation.

¹ Presented at the Conference, "Regulation of Gene Expression in Development and Neoplasia," June 2 to 5, 1976, Santa Ynez, Calif. Aided in part by Grants-in-Aid CA-12924, CA-13332, K6-18453 of the National Cancer Institute, NIH, USPHS, Bethesda, Md. The support of the Council for Tobacco Research, New York, N. Y. (Grant 935-M-2), is gratefully appreciated.

² Presenter.