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Genes involved in tumor invasion and metastasis are differentially modulated by estradiol and progestin in human breast‐cancer cells
Author(s) -
van den Brûle Frédéric A.,
Engel Jason,
StetlerStevenson William G.,
Liu FuTong,
Sobel Mark E.,
Castronovo Vincent
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910520426
Subject(s) - endocrinology , medicine , biology , laminin , metastasis , steroid hormone , estrogen , cancer cell , progesterone receptor , receptor , cancer research , estrogen receptor , breast cancer , hormone , cancer , extracellular matrix , microbiology and biotechnology
Invasion of basement membranes by cancer cells is a critical step in metastasis, which requires the coordinated expression of specific genes such as laminin receptors and metalloproteinases. Estradiol and progesterone modulate the clinical progression of steroid‐sensitive breast cancers; however, little is known about the molecular regulation of the invasive phenotype by these hormones. We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020 on the expression of 2 non‐integrin laminin binding proteins, the 67‐kDa laminin receptor (67LR) and HLBP31 as well as the 72‐kDa type‐IV collagenase (MMP‐2) and its inhibitor, TIMP‐2, in steroid‐receptorpositive (T47D and MCF‐7) and ‐negative (MDA‐MB 231) human breast‐cancer cells. The relative steady‐state level of 67LR mRNA was increased 2‐ to 3‐fold by estradiol in both MCF‐7 (p < 0.001) and T47D (p < 0.001) cells, also by R5020, alone or in combination with estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF‐7 cells. HLBP31 mRNA and protein levels were increased 2‐ to 3‐fold (p < 0.001) by R5020 alone or in combination with estradiol. but not by estradiol alone. None of the steroid treatments affected the expression or activity of MMP‐2. Interestingly, however, TIMP‐2 mRNA levels and protein expression in MCF‐7 and T47D cells were 50% down‐regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol, but not by treatment with estradiol alone. None of these genes were modulated in steroid‐independent MDA‐MB231 cells. The data suggest that estradiol and progesterone might act as coordinators regulating specific genes in the steroid‐sensitive breast‐cancer cell, leading to the acquisition of the metastatic phenotype. © 1992 Wiley‐Liss, Inc.