Tamoxifen stimulates human papillomavirus type 16 gene expression and cell proliferation in a cervical cancer cell line.
The widely adopted use of tamoxifen as a chemotherapeutic agent is primarily based on its inhibition of cancer cell growth. However, we report that tamoxifen at low concentrations (10(-9) and 10(-11) M) causes stimulation of cell proliferation in a cervical cancer cell line, SFR. The facts that SFR cells do not contain estrogen receptors and are estrogen nonresponsive imply the existence of an antiestrogen-specific binding protein and suggest that the effect of tamoxifen is possibly mediated through a pathway other than estrogen receptors. Tamoxifen at low concentrations stimulated human papillomavirus type 16 (HPV-16) gene transcription and E7 protein production. Levels of HPV-16 mRNA and E7 protein reached a peak at approximately 2-4 h after tamoxifen treatment, persisted for several hours, and subsequently decreased to their prestimulation levels by about 24 h after treatment. Our results indicate for the first time that tamoxifen stimulates cell proliferation of cervical cancer cells, and we suggest that the enhanced HPV-16 mRNA and E7 protein levels are probably responsible.
Hwang
J Y
JY
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Lin
B Y
BY
Tang
F M
FM
Yu
W C
WC
D002455:Cell Division / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger / Q000032:analysis; D011955:Receptors, Drug; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000382:microbiology / Q000473:pathology*
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D011955:Receptors, Drug; D011960:Receptors, Estrogen; C059731:oncogene protein E7, Human papillomavirus type 16; D013629:Tamoxifen