Chung Lab - University of Houston
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Center for Nuclear Receptors and Cell Signaling

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Chung Lab

Sanghyuk Chung, Ph.D.

Associate Professor
Department of Biology and Biochemistry

Office: SERC, 3008
Contact: schung@uh.edu - 832-842-8181

Figure

Mechanisms by which nuclear receptors modulate HPV-associated cancers and expression of HPV oncogenes
Human papillomaviruses (HPVs) cause various human cancers including those in uterine cervix and head/neck. The tumorigenic potential of HPV mainly stems from viral oncogenes E6 and E7, which inactivate p53 and pRb, respectively. Evidence indicates that steroid hormones regulate expression of E6 and E7, which may have implication in HPV-induced carcinogenesis. Studies using the HPV transgenic mice expressing E6 and E7 have demonstrated that HPV is not sufficient and other cofactors are required for HPV-associated cancers. Specifically, estrogen and its receptor ERalpha are required for the development of cervical cancer in the HPV transgenic mice. We also demonstrated that progesterone and its receptor inhibit cervical cancer. It is important to note that these effects are independent of their potential to regulate expression of E6 and E7. One of our research goals is to understand a molecular mechanism by which ERalpha and progesterone receptor modulate cervical cancer using HPV transgenic mouse model and orthotopic xenograft mouse model. We recently established a novel HPV transgenic mouse expressing E6/E7 and luciferase reporter under the control of HPV enhancer/promoter. This new mouse model will be useful to study a mechanism by which hormone receptors regulate expression of HPV oncogenes in vivo. We also explore a role of nuclear receptors in head and neck cancer using these unique mouse models. We anticipate that our studies will not only shed new light on pathogenesis of HPV-associated cancers but also identify therapeutic targets for such cancers.

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Funding

CPRIT NCI University of Houston Golfers Against Cancer

Sanghyuk Chung

Sanghyuk Chung, Ph.D.
Associate Professor

Department of Biology and Biochemistry
University of Houston
Houston, Texas 77204-5001

Office: SERC, 3008
Phone: 832-842-8181
schung@uh.edu

Ishmael Tetteh

Ishmael Tetteh
Graduate Student

iltetteh@cougarnet.uh.edu

Sasha Aiurova

Sasha Aiurova
Intern

aaiurova@cougarnet.uh.edu

Phoung V Le
Intern
pvle@cougarnet.uh.edu

  1. S.A. Lee, C. Ho, M. Troxler, C.Y. Lin, and S.H. Chung. (2021) Non-metabolic Functions of PKM2 Contribute to Cervical Cancer Cell Proliferation Induced by the HPV16 E7 Oncoprotein. Viruses. 13:433.
  2. Y. Park, S. Baik, C. Ho, C.Y. Lin, and S.H. Chung. (2021). Progesterone Receptor Is a Haploinsufficient Tumor Suppressor Gene in Cervical Cancer. Molecular Cancer Research. 19:42-47.
  3. Baik S, Mehta FF, Chung SH. (2019). Medroxyprogesterone Acetate Prevention of Cervical Cancer through Progesterone Receptor in a Human Papillomavirus Transgenic Mouse Model, Am. J. Pathol. 189: 2459-2468.
  4. J. Son, Y. Park, and S. H. Chung. (2018). Epithelial Oestrogen Receptor α Is Dispensable for the Development of Oestrogen-Induced Cervical Neoplastic Diseases, J. Pathol. 245:147-152.
  5. W. Chen, T. Shimane, S. Kawano, A. Alshaikh, S. Kim, S. H. Chung, R. H. Kim, K. Walentin, K. M. Schmidt-Ott, and M. K. Kang. (2018). Human Papillomavirus 16 E6 Induces FoxM1B in Oral Keratinocytes Through GRHL2, J. Dent. Res. 97:795-802.
  6. Mehta FF, Baik S and Chung SH. 2017. Recurrence of cervical cancer and its resistance to progestin therapy in a mouse model. Oncotarget. 8:2372-2380.
  7. Mehta FF, Son J, Hewitt SC, Jang E, Lydon JP, Korach KS and Chung SH. 2016. Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus. Oncotarget. 7:17455-17467.
  8. Chung SH, Targeting female hormone receptors as cervical cancer therapy. (2015) Trends Endocrinol Metab. 26:399-401.
  9. Spurgeon ME, Chung SH and Lambert PF. 2014. Recurrence of Cervical Cancer in Mice after Selective Estrogen Receptor Modulator Therapy. Am. J. Pathol. 184: 530-540.
  10. Son J, Park JW, Lambert PF and Chung SH. 2014. Requirement of Estrogen Receptor Alpha DNA-Binding Domain for HPV Oncogene-Induced Cervical Carcinogenesis in Mice. Carcinogenesis. 35: 489-496.
  11. Yoo Y. A., Son, J., Mehta, F. F., DeMayo, F. J., Lydon, J. P., and Chung, S. H. 2013. Progesterone Signaling Inhibits Cervical Carcinogenesis in Mice. Am J Pathol. 183: 1679-1687 (issue highlight)
  12. Ivanova, M. M., Radde, B. N., Son, J., Mehta, F. F., Chung, S. H., and Klinge, C. M.* 2013. Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus. J Mol Endocrinol. 51: 233-246
  13. Chung, S. H., Shin, M. K., Korach, K. S., and Lambert, P.F. 2013. Requirement for Stromal Estrogen Receptor Alpha in Cervical Neoplasia. Horm Cancer. 4: 50-59.
  14. Bonilla-Delgado J., Bulut, G., Liu, X., Cortés-Malagón, E. M., Schlegel, R., Flores-Maldonado, C., Contreras, R. G., Chung, S. H., Lambert, P. F., Uren, A., and Gariglio, P. 2012. The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/beta-catenin Pathway in Skin Epidermis in vivo. Mol. Cancer Res. 10: 250-258. (Cover)
  15. Chung SH, Franceschi S, Lambert PF., Estrogen and ERalpha: culprits in cervical cancer? (2010) Trends Endocrinol Metab. 21:504-11.
  16. Chung, S. H. & Lambert, P. F. 2009. Prevention and Treatment of Cervical Cancer in Mice Using Estrogen Receptor Antagonists. Proc. Natl. Acad. Sci. USA. 106: 19467-19472. (In This Issue)
  17. Chung, S. H., Wiedmeyer, K., Shai, A., Korach, K. S., Lambert, P. F. 2008. Requirement for Estrogen Receptor Alpha in a Mouse Model for Human Papillomavirus-Associated Cervical Cancer. Cancer Res. 68: 9928-9934. (Issue Highlight)
  18. Chung, S. H., Weiss, R. S., Frese, K. K., Prasad, B. V. V., and Javier, R. T. 2008. Functionally Distinct Monomers and Trimers Produced by a Viral Oncoprotein. Oncogene. 27: 1412-1420.
  19. Chung, S. H., Frese, K. K., Weiss, R. S., Prasad, B. V. V., and Javier, R. T. 2007. A New Crucial Protein-Interaction Element That Targets the Adenovirus E4-ORF1 Oncoprotein to Membrane Vesicles. J. Virol. 81: 4787-4797.
  20. Frese, K. K., Latorre, I. J., Chung, S. H., Caruana, G., Bernstein, A., Jones, S. N., Donehower, L. A., Justice, M. J., Garner, C. C., and Javier, R. T. 2006. Oncogenic Function for the Dlg1 Mammalian Homolog of the Drosophila Discs-Large Tumor Suppressor. EMBO J. 25: 1406-1417