Down-regulation of tenascin expression by antiprogestins during terminal differentiation of rat mammary tumors

• Published in: Cancer research (Chicago, Ill.) Ill.), 1992-09, Vol.52 (17), p.4642
• Main Authors: Vollmer, G, Michna, H, Ebert, K, Knuppen, R
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cell Adhesion Molecules, Neuronal - metabolism; Cell Differentiation - drug effects; Extracellular Matrix Proteins - metabolism; Female; Gonanes - pharmacology; Immunohistochemistry; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Methylnitrosourea; Ovariectomy; Progesterone - antagonists & inhibitors; Rats; Tamoxifen - pharmacology; Tenascin; Uterus - metabolism
• ISSN: 0008-5472

Studies on tenascin expression in hormonally dependent growing tissues of breast and endometrium suggested that its expression parallels the progression of normal or malignant proliferative alteration of the tissue. With the study presented here we addressed the question of whether antiprogestin-induced terminal differentiation down-regulates tenascin expression. By comparative immunolocalization of tenascin in sections of untreated 7,12-dimethylbenz[alpha]anthracene-induced tumors, tumors grown in ovariectomized animals, tamoxifen-treated tumors, and antiprogestin-treated tumors, we obtained the following results. (a) The entire extracellular space of the stromal mesenchyme was filled by tenascin immunoreactivity in cases of untreated control tumors. (b) Both ovariectomy and antiestrogen treatment with tamoxifen did not affect the overall staining pattern and resulted in a slight increase of the arbitrarily judged staining intensity. (c) Within antiprogestin-treated tumors tenascin-like immunoreactivity predominantly was restricted to fiber-like, collagenous connective tissue structures, which appeared in the stromal compartment as a result of the antiprogestin treatment. In large areas of the tumor composed of apparently secretory active tumor cells we failed to immunolocalize tenascin. Our results provide further evidence that expression of tenascin reflects both benign and malignant proliferative alterations of the tissue, whereas its down-regulation is correlated to differentiation of the tissue. Additionally, evidence is provided that the mechanism of tumor growth inhibition by antiprogestins indeed is induction of terminal differentiation of tumor cells.