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Expression of a Parathyroid Hormone-Like Protein and Its Receptor during Differentiation of Embryonal Carcinoma Cells

Endocrine Unit, Veterans Administration Medical Center and the Departments of Medicine and Physiology, University of California San Francisco, California 94121

Address requests for reprints to: Dr. Samuel D. H. Chan, Endocrine Unit, Veterans Administration Medical Center (111N), 4150 Clement Street, San Francisco, California 94121.

Abstract

Differentiation of mouse embryonal carcinoma cells to the parietal endoderm phenotype is associated with expression of PTH-responsive adenylate cyclase. A PTH-like protein (PLP), which binds to PTH receptors and activates adenylate cyclase in classical PTH target cells was recently isolated and cloned. We assessed whether the parietal endoderm phenotype is associated with the expression of PLP or its receptor. A 1.4-kilobase PLP transcript was detected in the mouse parietal endoderm cell line PYS-2. No hybridizing transcripts were evident in undifferentiated mouse embryonal carcinoma cells PSA-1 or F9. However, differentiation of these cells to parietal endoderm, either spontaneously (PSA-1) or by treatment with retinoic acid and dibutyryl cAMP (F9), resulted in expression of the 1.4-kilobase PLP message. Undifferentiated F9 cells displayed negligible specific binding of [¹²⁵1]PLP-(1-34)amide. When F9 cells were induced to differentiate to parietal endoderm, specific binding sites for [¹²⁵I]PLP-(1–34)amide were expressed in parallel with PLP-responsive adenylate cyclase. These receptors, like those in classical PTH target tissues, displayed identical affinity (K_d = 5.2 nM) for bPTH-(1–34) and hPLP-(1–34)amide; with binding capacity (B_max) of 6.6 x 10⁴ sites/cell. In the presence of retinoic acid, exogenous PLP substituted for dibutyryl cAMP in a concentration-dependent fashion in promoting the differentiation of F9 cells to parietal endoderm. Thus, both PLP mRNA and PLP receptors coupled to adenylate cyclase are expressed during the differentiation of mouse embryonal carcinoma cells. Increased cAMP levels produced by autocrine stimulation of PLP receptors by PLP may contribute to differentiation of embryonal carcinoma cells into parietal endoderm.

FOOTNOTES

This work was supported by National Research Service Award DK-07418, NIH Grants CA-34738 and DK-35323, and the Research Service of the Department of Veterans Affairs.

Received for publication December 7, 1989. Revision received January 26, 1990. Accepted for publication January 26, 1990.

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