title: Tamoxifen regulation of ectocervical cell differentiation.
abstract: OBJECTIVE
  To determine the effects of tamoxifen on the growth and differentiation of normal human cervical cells and compare those effects with those of a synthetic estrogen, diethylstilbestrol (DES). In addition, the effects of these compounds on immortalized cervical cells and cervical tumor cells were ascertained.
  
  
  METHODS
  Growth curves were used to determine the effects on cell proliferation. The expression of several proteins was used to determine the effects on cell differentiation. Binding assays and Western analysis were used to determine estrogen receptor levels.
  
  
  RESULTS
  Both tamoxifen and DES inhibited the proliferation of normal cervical cells. This growth inhibition was coincident with an increase in cell differentiation as determined by cornified envelope formation. The increase in envelope number was not accompanied by an increase in involucrin or cornifin, two protein precursors of the envelope. The activity of transglutaminase, which enzymatically incorporates precursor proteins into the envelope, was not stimulated following treatment. Diethylstilbestrol did not alter the growth or differentiation of the human papillomavirus 16-immortalized cell line ECE16-1 or any of the cervical tumor cell lines. Of all the immortalized or cancer cell lines, only Caski cells were growth inhibited by tamoxifen. Normal ectocervical epithelial cells and Caski cells expressed the high-affinity 56-kDa estrogen receptor, but 3H-estradiol binding was not detected in cell extracts from either ME180 or ECE16-1 cells. Nevertheless, extracts from ME180 cells contained an immunoreactive band at the appropriate molecular weight for the estrogen receptor.
  
  
  CONCLUSIONS
  These results suggest that tamoxifen and DES act similarly in normal cervical cells to promote cervical cell differentiation. However, because Caski cell growth was inhibited by tamoxifen and not DES, the effects of tamoxifen in these cells may be mediated by non-estrogen receptor mechanisms.
authors.affiliation: Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: D
authors.initials: D
authors.lastname: Macinga
authors.forename: V
authors.initials: V
authors.lastname: Jain
authors.forename: N
authors.initials: N
authors.lastname: Sizemore
authors.forename: G I
authors.initials: GI
authors.lastname: Gorodeski
authors.forename: R L
authors.initials: RL
authors.lastname: Eckert
authors.forename: E A
authors.initials: EA
authors.lastname: Rorke
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D027383:Papillomaviridae / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D014162:Transfection; D011503:Transglutaminases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol; D004054:Diethylstilbestrol; D011503:Transglutaminases