Progestins and danazol effect on cell-to-cell adhesion, and E-cadherin and alpha- and beta-catenin mRNA expressions.
The first step of invasion and metastasis is the detachment of cancer cells in the primary tumor, which is mainly controlled by the function in the adherens junction, consisting of E-cadherin associated proteins (E-cadherin, alpha- and beta-catenins, vinculin, alpha-actinin, and actin). The cell-to-cell aggregation activity and the expressions of E-cadherin, and alpha- and beta-catenin mRNAs in Ishikawa cells of well-differentiated endometrial cancer were significantly suppressed by estrogen. These suppressions were reversed by progesterone, medroxyprogesterone acetate (MPA) and danazol. Proteins in the adherens junction appeared to be expressed intact and to be functional in Ishikawa cells. Persistent estrogen predominant milieu might contribute to the detachment of well-differentiated endometrial cancer cells, leading to spreading of those cells, while progestins and danazol protect estrogen-induced spreading of those cells.
Fujimoto
J
J
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu City 500, Japan.
Ichigo
S
S
Hori
M
M
Morishita
S
S
Tamaya
T
T
D000230:Adenocarcinoma / Q000473:pathology; D015820:Cadherins / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects*; D002449:Cell Aggregation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003613:Danazol / Q000494:pharmacology*; D016889:Endometrial Neoplasms / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004965:Estrogen Antagonists; D011372:Progestins; D012333:RNA, Messenger; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D003613:Danazol