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Regulation of Anchorage-independent Growth by Thyroid Hormone in Type 5 Adenovirus-transformed Rat Embryo Cells¹

Department of Microbiology, Cancer Center/Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, New York 10032 [L. E. B., P. B. F.], and Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City, Iowa 52242 [D. L. G.]

We have analyzed the effect of triiodothyronine and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on expression of the transformed phenotype, as monitored by agar clonigenicity, in a single cell clone of type 5 adenovirus-transformed Sprague-Dawley rat embryo cells, E11, and a nude mouse tumor-derived E11 subclone, E11-NMT. When grown in medium devoid of thyroid hormone, the cloning efficiency of E11 and E11-NMT cells was 1 and 19%, respectively, whereas continuous exposure to triiodothyronine (1 nM) resulted in cloning efficiencies of 3% for E11 cells and 50% for E11-NMT cells. In addition, the average size of agar colonies was larger when cells were grown in the presence of thyroid hormone. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (100 ng/ml) could substitute for triiodothyronine, resulting in agar cloning efficiencies similar to those found in cells grown in medium containing this hormone. In contrast, the presence or absence of triiodothyronine did not alter the population doubling time or saturation density of E11 or E11-NMT cells. Although both normal Sprague-Dawley rat embryo and type 5 adenovirus-transformed E11 and E11-NMT cells contained nuclear triiodothyronine receptors with similar affinities, the number of thyroid hormone receptors was lower in the virally transformed cells. Growth of E11-NMT cells in medium containing or lacking thyroid hormone did not alter the ability of these cells to bind ¹²⁵I-labeled epidermal growth factor. In addition, the quantity of transforming polypeptide growth factor(s), secreted into serum-free medium, which was capable of competing with labeled epidermal growth factor for binding to its receptors on a cloned Fischer rat embryo cell line (CREF) and inducing agar growth in normally anchorage-dependent CREF cells was similar in E11-NMT cells grown in medium containing or depleted of thyroid hormone. Growth of E11-NMT cells in medium lacking triiodothyronine did not alter transcriptional rates of RNA produced by the viral transforming genes, E1a and E1b, or the level of a M_r 21,000 polypeptide encoded by E1b. These findings indicate that thyroid hormone can modulate expression of the transformed phenotype in type 5 adenovirus-transformed cells without directly modifying expression of type 5 adenovirus-transforming genes.

¹ These studies were supported by National Cancer Institute Grants CA-35675 and CA-36483.

² Present address: The Rockefeller University, New York, NY 10021.

³ To whom requests for reprints should be addressed.

Received 3/13/85. Revised 8/13/85. Accepted 8/22/85.