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Effect of human papillomavirus 16 immortalization on retinoic acid regulation of epidermal growth factor responsiveness and differentiation of normal ectocervical epithelial cells

Sizemore, Nywana
http://rave.ohiolink.edu/etdc/view?acc_num=case1058216018

Abstract Details

1995, Doctor of Philosophy, Case Western Reserve University, Environmental Health Science.
This study was based on the hypothesis that human papillomavirus (HPV) type 16 immortalization of normal human ectocervical epithelial (ECE) cells alters the retinoic acid regulation of normal cervical cell differentiation and epidermal growth factor (EGF) stimulated growth. The rational for this study is that it might explain the anti-neoplastic effect of retinoic acid on HPV positive cervical lesions. As a model system to study normal cervical cell function, primary ectocervical epithelial (ECE) cells were cultured from cervical tissue explants on feeder layers. Under these conditions, ECE cells retain in vivo-like keratin expression, hormonal responsiveness, and differentiation status in vitro. Human papillomavirus cell lines are produced from cultures of primary ECE cells using eukaryotic expression vectors containing the HPV type 16 genome. The ECE16-1, ECE16-D1, and ECE16-D2 cell lines are models of an HPV16-immortalized ectocervical cell. The significant findings were: (1) Immortalization of normal ECE cells by HPV type 16 induces increased EGF receptor expression and raises growth sensitivity to EGF. (2) Retinoic acid, while not effecting growth of normal ECE cells, inhibits EGF stimulated growth of HPV immortalized cell lines in a dose dependent manner. (3) Retinoic acid growth suppression of ECE16-1 and ECE16-D1 cell lines was preceded by a reduction of epidermal growth factor (EGF) receptor binding, protein levels, mRNA levels, and promoter activity. Suppression of the EGF receptor was not detected in the normal ECE or the ECE16-D2 cell line. (4) Transient cotransfection of the HPV-16 E6/E7 genes with the EGF receptor promoter in normal ECE cells stimulates activity of the promoter two- to three-fold. (5) Retinoids decrease normal ectocervical epithelial cell differentiation by changing transglutaminase activity and keratin gene expression. Immortalization by HPV type 16 does not alter the effect of retinoic acid on transglutaminase or keratin expression, but the immortalized cells seem to have a heightened sensitivity to retinoids. Based on these results I conclude, the effect of retinoic acid in vivo may be to maintain normal ectocervical epithelial cell physiology while inhibiting the growth and progression of HPV-positive lesions.
Ellen Rorke (Advisor)
150 p.
Biology, Cell
human papillomavirus 16 immortalization retinoic acid regulation epidermal growth factor responsiveness differentiation normal ectocervical epithelial cells

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Citations

  • Sizemore, N. (1995). Effect of human papillomavirus 16 immortalization on retinoic acid regulation of epidermal growth factor responsiveness and differentiation of normal ectocervical epithelial cells [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1058216018

    APA Style (7th edition)

  • Sizemore, Nywana. Effect of human papillomavirus 16 immortalization on retinoic acid regulation of epidermal growth factor responsiveness and differentiation of normal ectocervical epithelial cells. 1995. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1058216018.

    MLA Style (8th edition)

  • Sizemore, Nywana. "Effect of human papillomavirus 16 immortalization on retinoic acid regulation of epidermal growth factor responsiveness and differentiation of normal ectocervical epithelial cells." Doctoral dissertation, Case Western Reserve University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=case1058216018

    Chicago Manual of Style (17th edition)

case1058216018
439
© 1995, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.