Histological, immunohistochemical, and ultrastructural features of a rat medullary thyroid carcinoma transfected with a corticotropin-releasing hormone cDNA expression vector

Meora Feinmesser, Sylvia L. Asa, Kaiman Kovacs, Bernard A. Roos, Malcolm J. Low

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Clonal cell lines producing corticotropin-releasing hormone (CRH) have been generated by transfection of the W2 rat medullary thyroid carcinoma (MTC) cell with a CRH-encoding CMV/ SV40 expression vector. Here, we report the morphological, immunohistochemical, and ultrastructural features of rat tumors derived by implantation of CRH-producing W2CRH-7 cells and compare them with non-CRH-producing W2 MTCs. Both types of tumors grew rapidly and consisted of sheets and nests of pleomorphic cells infiltrating adjacent adipose tissue. Immunohistochemistry revealed CRH in only W2CRH-7 tumors; scattered cells in these tumors also were immunoreactive for chromogranin and for vasoactive intestinal peptide. Otherwise, the two tumor types exhibited similar profiles of various neuroendocrine markers, including neuron-specific enolase, synaptophysin, calcitonin, and somatostatin. Ultrastructurally, the tumors contained abundant dilated rough endoplasmic reticulum, a prominent Golgi apparatus, and numerous lysosomes. Very few secretory granules were noted in the W2 tumors; by contrast, secretory granules, although still not numerous in the majority of W2CRH-7 cells, were more abundant in scattered cells of those tumors. The positive immunostaining for CRH is consistent with the observations of increased plasma CRH and pituitary-adrenal activation induced by these transplanted tumors. This system provides a valuable model for CRH excess mimicking tumoral CRH-dependent Cushing's syndrome in human patients.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalEndocrine Pathology
Volume3
Issue number1
DOIs
StatePublished - Mar 1 1992

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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