title: The rat hepatic lectin-1 subunit of the asialoglycoprotein receptor is upregulated by thyrotropin and downregulated by neoplastic transformation of thyroid cells.
abstract: We have recently shown that the rat hepatic lectin (RHL)-1 subunit of the asialoglycoprotein receptor (ASGPr) is expressed in the PC C13 differentiated thyroid cell line. To investigate in vivo the expression of RHL-1 and the ability of thyrotropin (TSH) to modulate its expression, reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot assays have been performed on thyroid extracts from rats treated with thyroxine (T4) or propylthiouracil (PTU), each of which modulates TSH levels. It is shown that RHL-1 expression is down-regulated by T4 (which decreases serum TSH) and upregulated by PTU (which increases serum TSH), at both mRNA and protein levels. The sensitivity of RHL-1 to neoplastic transformation of thyroid cells has been investigated. The RHL-1 expression pattern has been studied in PC C13 thyroid cells transformed by several oncogenes that induce different degrees of malignancy and dedifferentiation. RT-PCR and Western blot assays show that RHL-1 expression progressively decreases as PC C13 cells acquire a more transformed phenotype. Expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, a housekeeping gene used as internal control to normalize RHL-1 mRNA content, exhibits no variations in the different PC C13 cell lines used. In addition, we show that both native and asialo-thyroglobulin (Tg) bind RHL-1 in vitro, and native Tg binds RHL-1 on the surface of PC C13 cells. After thyroid cells transformation, the surface expression of RHL-1 is inhibited in a measure that correlates with the mRNA and protein levels. Therefore, the RHL-1 inhibition at the mRNA, protein and plasma membrane expression follows a gradient that parallels the progressive acquisition of the fully transformed phenotype in the PC C13 system. The results reported in the present article, together with our previous data, suggest that RHL-1 expression could be regulated, at least in part, by the same transcription factors involved in the expression of the other molecules characteristic of the thyroid differentiated state.
authors.affiliation: Centro di Endocrinologia ed Oncologia Sperimentale G Salvatore, CNR, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pacifico
authors.forename: D
authors.initials: D
authors.lastname: Liguoro
authors.forename: N
authors.initials: N
authors.lastname: Montuori
authors.forename: S
authors.initials: S
authors.lastname: Mellone
authors.forename: V
authors.initials: V
authors.lastname: Macchia
authors.forename: S
authors.initials: S
authors.lastname: Formisano
authors.forename: E
authors.initials: E
authors.lastname: Consiglio
authors.forename: B
authors.initials: B
authors.lastname: Di Jeso
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation / Q000502:physiology*; D008297:Male; D011441:Propylthiouracil / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D037263:Asialoglycoprotein Receptor; D011956:Receptors, Cell Surface; D011441:Propylthiouracil; D013972:Thyrotropin; D013974:Thyroxine