Modulation of laminin receptor expression by estrogen and progestins in human breast cancer cell lines.
The effects of estradiol and two synthetic progestins (ORG2058 and R5020) on the expression of the high-affinity, metastasis-associated laminin receptor in two human breast carcinoma cell lines were examined. The T47D cell line contains estrogen and progesterone receptors, but the MDA-MB 231 cell line lacks both receptors. Treatment of T47D cells with 10(-9) M estradiol alone results in a three-fold increase (P less than or equal to .05) in the steady-state level of laminin receptor mRNA determined by RNA blot analysis as well as in cell-surface, laminin receptor expression that is evaluated by immunofluorescence. No effects of estradiol on the receptor-negative MDA-MB 231 cells were observed. Untreated and steroid-treated MDA-MB 231 cells had higher levels of laminin receptor mRNA than did untreated or estradiol-treated T47D cells. A more dramatic increase (five-fold; P less than or equal to .005) of mRNA and cell-surface expression in T47D cells was observed after treatment with estradiol plus 10(-8) M progestin or with progestin alone. Estradiol treatment also increased chemotaxis and haptotaxis of T47D cells but not of MDA-MB 231 cells to laminin; it had no effect on the attachment of these latter cells to laminin. Interestingly, treatment with estradiol plus progestin or progestin alone significantly increased the attachment of T47D cells to laminin but did not have an effect on either haptotaxis or chemotaxis to laminin. These results suggest that the various cell-laminin interactions are mediated by different mechanisms. The augmentation of laminin receptor mRNA by estrogen and progesterone treatment in hormone receptor-positive cells, but not in cells that lack these receptors, may relate functionally to the difference in the clinical aggressiveness between classes of breast cancers.
Castronovo
V
V
Tumor Invasion and Metastasis Section, National Cancer Institute, Bethesda, MD 20892.
Taraboletti
G
G
Liotta
L A
LA
Sobel
M E
ME
D001943:Breast Neoplasms / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000187:drug effects; D017474:Receptors, Laminin; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007797:Laminin; D011282:Pregnenediones; D045167:Progesterone Congeners; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017474:Receptors, Laminin; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D004958:Estradiol; D011397:Promegestone