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Human papillomavirus type 16 E6 and E7 oncogene expression in relation to host cell growth and differentiation

Choo, Chee-Keong
http://rave.ohiolink.edu/etdc/view?acc_num=case1057943758

Abstract Details

1994, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
In chapter II and III, we examined the effects of extracellular calcium regulation of cervical cell differentiation and HPV16 E6/E7 expression in response to calcium induced differentiation in a HPV16 immortalized cervical cell line, ECE16-1, and a HPV16-positive cervical carcinoma cell line, CaSki. ECE 16-1 and CaSki cells respond to increased calcium with increased levels of mRNA encoding differentiation markers(K13, involucrin and TG). The overall differentiation marker expression in CaSki cells is lower than in ECE16-1 cells. Protein levels change directly with the change in their corresponding mRNA, suggesting that mRNA level determines protein concentration. Transcription runoff experiments on ECE 16-1 cells indicate that the increased mRNA does not result from new synthesis. Parallel studies in ECE16-1 and CaSki cells indicate that expression of the HPV16 E6/E7 oncogene is not regulated by extracellular calcium induced differentiation, suggesting that differentiation-independent expression of E6/E7 levels is a property of both tumorigenic (CaSki) and non-tumorigenic (ECE16-1) HPV16-positive cervical epithelial cells. In chapter IV we evaluate the effects of all-trans retinoic acid (RA) on growth, dif ferentiation, expression of c-myc, and expression of HPV E6/E7 in HPV16 immortalized cervical cells. Our results indicate that the differentiation markers are suppressed by retinoids in HPV16 immortalized cervical cell lines. They are more sensitive to the effects of retinoic acid than normal cells. The level of HPV16 transcript encoding E6/E7 is not significantly suppressed by 1 uM RA in ECE 16-1 cells, but is suppressed in ECE16-D1 and ECE16-D2 cells. In addition, a transient rise in HPV transcripts encoding E6/E7 is observed at intermediate (10 and 100 nM) RA concentrations in ECE16-1 and ECE16-D2 cells. c-myc mRNA levels are elevated (5.5-fold) in HPV16-immortalized cells relative to normal cells, and are not regulated by RA. RA does not regulate proliferation in ECE16-D1 or ECE16-D2 cells but slightly suppress ECE16-1 cell growth. The levels of E6/E7 can be regulated independent of cell growth, suggesting that E6/E7 mRNA levels can be regulated independent of effects on cell proliferation in confluent cultures. In chapter V, we demonstrate that the responses of the cells fall into four groups. In the first group, E6/E7 RNA level is directly correlated with proliferation rate and inversely correlated with p53 level. In group two, E6/E7 level is directly correlated with proliferation rate, but p53 levels are not regulated. In group three, p53 level is inversely correlated with proliferation rate, but E6/E7 RNA level is not regulated. In the fourth group there is no regulation of E6/E7 level, p53 level or proliferation. RB protein levels were also assayed and found not to be regulated by RA, IFNγ or TGFβ1 in any of the cell lines. These results indicate that the response of cells to agents that regulate cell differentiation and proliferation may not always be mediated via effects on p53 and/or E6/E7 RNA level and suggest that other pathways may be as important in some circumstances. (Abstract shortened by UMI.
Richard Eckert (Advisor)
259 p.
Human papillomavirus 16 E6 E7 oncogene expression relation host cell growth differentiation

Recommended Citations

Citations

  • Choo, C.-K. (1994). Human papillomavirus type 16 E6 and E7 oncogene expression in relation to host cell growth and differentiation [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1057943758

    APA Style (7th edition)

  • Choo, Chee-Keong. Human papillomavirus type 16 E6 and E7 oncogene expression in relation to host cell growth and differentiation. 1994. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1057943758.

    MLA Style (8th edition)

  • Choo, Chee-Keong. "Human papillomavirus type 16 E6 and E7 oncogene expression in relation to host cell growth and differentiation." Doctoral dissertation, Case Western Reserve University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=case1057943758

    Chicago Manual of Style (17th edition)

case1057943758
433
© 1994, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.