Endocrine

, Volume 17, Issue 3, pp 233–239

Estrogen stimulates expression of p21Waf1/Cip1 in mouse uterine luminal epithelium

Article

Abstract

p21Waf1/Cip1 was originally identified as an inhibitor of the cell cycle. Recent evidence suggests that it can act as a positive regulator of the cell cycle under the influence of some growth stimulators. We investigated the effects of ovarian steroids on the expression of p21, DNA synthesis, and mitosis in the uterus. Capsules containing 17β-estradiol (E2) were subcutaneously implanted in ovariectomized mice that were sacrificed on different days. Their uteri were collected for p21 immunohistochemical staining. To study mitosis and DNA synthesis, colchicine and bromodeoxyuridine (BrdU) were injected into mice 3 or 5 h before sacrifice. The results showed that p21 expression, BrdU incorporation, and the mitotic index in uterine luminal epithelium increased 1 to 2 d after E2 stimulation and then declined to basal levels between d 3 and 6. Furthermore, cotreatment with progesterone (P4) and E2 suppressed both p21 expression and the DNA synthesis stimulated by E2 alone in uterine epithelial cells. Our results show that estrogen stimulates p21 expression and cell proliferation in uterine luminal epithelium and that cotreatment with P4 prevents both effects, suggesting that p21 may act as a positive cell-cycle regulator.

Key Words

p21 proliferation uterus estrogen 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pestell, R. G., Albanese, C., Reutens, A. T., Segall, J. E., Lee, R. J., and Arnold, A. (1999). Endocr. Rev. 20, 501–534.PubMedCrossRefGoogle Scholar
  2. 2.
    Sherr, C. J. and Roberts, J. M. (1995). Genes Dev. 9, 1149–1163.PubMedGoogle Scholar
  3. 3.
    El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., and Vogelstein, B. (1993). Cell 75, 817–825.PubMedCrossRefGoogle Scholar
  4. 4.
    Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K., and Elledge, S. J. (1993). Cell 75, 805–816.PubMedCrossRefGoogle Scholar
  5. 5.
    Waga, S., Hannon, G. J., Beach, D., and Stillman, B. (1994). Nature 369, 574–578.PubMedCrossRefGoogle Scholar
  6. 6.
    Li, R., Waga, S., Hannon, G. J., Beach, D., and Stillman, B. (1994). Nature 371, 534–537.PubMedCrossRefGoogle Scholar
  7. 7.
    Leonardo, A. D., Linke, S. P., Clarkin, K., and Wahl, G. M. (1994). Genes Dev. 8, 2540–2551.PubMedGoogle Scholar
  8. 8.
    Cayrol, C., Knibiehler, M., and Ducommun, B. (1998). Oncogene 16, 311–320.PubMedCrossRefGoogle Scholar
  9. 9.
    Steinman, R. A., Hoffman, B., Iro, A., Guillouf, C., Liebermann, D. A., and El-Houseini, M. E. (1994). Oncogene 9, 3389–3396.PubMedGoogle Scholar
  10. 10.
    Michieli, P., Chedid, M., Lin, D., Pierce, J. H., Mercer, W. E., and Givol, D. (1994). Cancer Res. 54, 3391–3395.PubMedGoogle Scholar
  11. 11.
    Mantel, C., Luo, Z., Canfield, J., Braun, S., Deng, C., and Broxmeyer, H. E. (1996). Blood 88, 3710–3719.PubMedGoogle Scholar
  12. 12.
    Crish, J. F., Bone, F., Balasubramanian, S., Zaim, T. M., Wagner, T., Yun, J., Roke, E. A., and Eckert, R. L. (2000). Carcinogenesis 21, 1031–1037.PubMedCrossRefGoogle Scholar
  13. 13.
    LaBaer, J., Garrett, M. D., Stevenson, L. F., Slingerland, J. M., Sandhu, C., Chou, H. S., Fattaey, A., and Harlow, E. (1997). Genes Dev. 11, 847–862.PubMedGoogle Scholar
  14. 14.
    Palazzo, J. P., Mercer, W. E., Kovatich, A. L., and McHugh, M. (1997). Hum. Pathol. 28, 60–66.PubMedCrossRefGoogle Scholar
  15. 15.
    Toki, T., Mori, A., Shimizu, M., Nikaido, T., and Fujii, S. (1998). Mol. Hum. Reprod. 4, 1157–1164.PubMedCrossRefGoogle Scholar
  16. 16.
    Yoshida, A., Newbold, R. R., and Dixon, D. (2000). Toxicol. Pathol. 28, 237–245.PubMedGoogle Scholar
  17. 17.
    Tan, J., Raja, S., Davis, M. K., Tawfik, O., Dey, S. K., and Das, S. K. (2002). Mech. Dev. 111, 99–113.PubMedCrossRefGoogle Scholar
  18. 18.
    Lu, S., Liu, M., Epner, D. E., Tsai, S. Y., and Tsai, M. J. (1999). Mol. Endocrinol. 13, 376–384.PubMedCrossRefGoogle Scholar
  19. 19.
    Waltregny, D., Leav, I., Signoretti, S., Soung, P., Lin, D., Merk, F., Adams, J. Y., Bhattacharya, N., Cirenei, N., and Loda, M. (2001). Mol. Endocrinol. 15, 765–782.PubMedCrossRefGoogle Scholar
  20. 20.
    Martin, L., Pollard, J. W., and Fagg, B. (1976). J. Endocr. 69, 103–115.PubMedGoogle Scholar
  21. 21.
    Quarmby, V. E. and Korach, K. S. (1984). Endocrinology 114, 694–702.PubMedCrossRefGoogle Scholar
  22. 22.
    Tong, W. and Pollard, J. W. (1999). Mol. Cell. Biol. 19, 2251–2264.PubMedGoogle Scholar
  23. 23.
    Wilson, J. W., Pritchard, D. M., Hickman, J. A., and Potten, C. S. (1998). Am. J. Pathol. 153, 899–909.PubMedGoogle Scholar
  24. 24.
    Geum, D., Sun, W., Paik, S. K., Lee, C. C., and Kim, K. (1997). Mol. Reprod. Dev. 46, 450–458.PubMedCrossRefGoogle Scholar
  25. 25.
    Altucci, L., Addeo, R., Cicatiello, L., Germano, P., Pacilio, C., Battista, T., Cancemi, M., Petrizzi, V. B., Bresciani, F., and Weisz, A. (1997). Endocrinology 138, 978–984.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhuang, Y., Sarca, D., Weisz, A., Altucci, L., Cicatiello, L., Rollerova, E., Tuohimaa, P., and Ylikomi, T. (2001). J. Steroid Biochem. Mol. Biol. 78, 193–199.PubMedCrossRefGoogle Scholar
  27. 27.
    Sheer, C. J. and Roberts, J. M. (1999). Genes Dev. 13, 1501–1512.Google Scholar
  28. 28.
    Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F., Roberts, J. M., and Sherr, C. J. (1999). EMBO J. 18, 1571–1583.PubMedCrossRefGoogle Scholar
  29. 29.
    Muraoka, R. S., Lenferink, A. E. G., Simpson, J., Brantley, D. M., Roebuck, L. R., Yakes, F. M., and Arteaga, C. L. (2001). J. Cell Biol. 153, 917–931.PubMedCrossRefGoogle Scholar
  30. 30.
    Weiss, R. H., Joo, A., and Randour, C. (2000). J. Biol. Chem. 275, 10,285–10,290.Google Scholar
  31. 31.
    Macleod, K., Sherry, N., Hannon, G., Beach, D., Tokino, T., Kinzler, K., Vogelstein, B., and Jacks, T. (1995). Genes Dev. 9, 935–944.PubMedGoogle Scholar
  32. 32.
    Lu, S., Jenster, G., and Epner, D. E. (2000). Mol. Endocrinol. 14, 753–760.PubMedCrossRefGoogle Scholar
  33. 33.
    Scholz, A., Truss, M., and Beato, M. (1998). J. Biol. Chem. 273, 4360–4366.PubMedCrossRefGoogle Scholar
  34. 34.
    Castro-Rivera, E., Samudio, I., and Safe, S. (2001). J. Biol. Chem. 276, 30,853–30,861.Google Scholar
  35. 35.
    Gartel, A. L. and Tyner, A. L. (1999). Exp. Cell Res. 246, 280–289.PubMedCrossRefGoogle Scholar
  36. 36.
    Cohen, P. E. and Milligan, S. R. (1993). J. Reprod. Fertil. 99, 219–223.PubMedCrossRefGoogle Scholar
  37. 37.
    McCormack, J. T. and Greenwald, G. S. (1974). J. Endocr. 62, 101–107.PubMedCrossRefGoogle Scholar
  38. 38.
    Shinohara, Y., Matsumoto, H., and Mori, T. (1997). In Vivo 11, 249–252.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Ming-Derg Lai
    • 1
  • Meei Jyh Jiang
    • 2
  • Lih-Yuh C. Wing
    • 1
  1. 1.Department of PhysiologyCollege of Medicine, National Cheng Kung UniversityTainanTaiwan
  2. 2.Department of Cell Biology and AnatomyCollege of Medicine, National Cheng Kung UniversityTainanTaiwan

Personalised recommendations