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Thyroid hormone regulates stromelysin expression, protease secretion and the morphogenetic potential of normal polarized mammary epithelial cells.
Author(s) -
LópezBarahona M.,
Fialka I.,
GonzálezSancho J.M.,
Asunción M.,
González M.,
Iglesias T.,
Bernal J.,
Beug H.,
Muñoz A.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb07098.x
Subject(s) - humanities , biology , library science , art , computer science
Stromelysins are a group of proteases which degrade the extracellular matrix and activate other secreted proteases. Stromelysin (ST)‐1 and ST‐2 genes are induced by tumor promoters, oncogenes and growth factors, and have been involved in acquisition of the malignant phenotype. We show here that the thyroid hormone (T3) increases ST‐1 and ST‐2 expression in a non‐transformed mouse mammary epithelial cell line (EpH4) in a way that is dependent on the level of thyroid receptor/c‐erbA (TR alpha‐1) expression. In agreement with this, T3 increases the secreted stromelysin activity and enhances the gelatinolytic activity of type IV collagenase. We have also demonstrated that T3 affects the epithelial polarity of EpH4 cells, diminishing the transepithelial electrical resistance of monolayers cultured on permeable filters, causing an abnormal distribution of polarization markers and the disruption of the organized 3‐D structures formed by these cells in type I collagen gels. These results indicate that the ligand‐activated TR alpha‐1 plays an important role in regulating the morphogenetic and invasive capacities of mammary epithelial cells. Because the c‐erbA locus is altered in several types of carcinoma, an altered or deregulated TR alpha‐1 expression may also be important for breast cancer development and metastasis.