Skip NavigationSkip to Content
Return Return to Search Results

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

  1. Author:
    Yan, X. D.
    Yin, J.
    Yao, H. Y.
    Mao, N.
    Yang, Y. L.
    Pan, L. Y.

  2. Author Address

    [Yan, Xuedong; Yin, Jie; Pan, Lingya] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing 100730, Peoples R China. [Yan, Xuedong; Yin, Jie; Pan, Lingya] Peking Union Med Coll, Beijing 100730, Peoples R China. [Yao, Huiyu; Mao, Ning] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Cell Biol, Beijing 100730, Peoples R China. [Yang, Yili] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.;Pan, LY, Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, 1 Shuai Fu Yuan,Wang Fu Jing St, Beijing 100730, Peoples R China.;lingyapan@hotmail.com
    1. Year: 2010
    2. Date: Feb
  2. Journal: Cancer Research
    1. 70
    2. 4
    3. Pages: 1616-1624
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    Resistance to platinum drugs has emerged as a major obstacle in the treatment of ovarian cancers. Through proteomic analysis, we have found that the expression of annexin A3, a member of the Ca2+ and phospholipid-binding annexin family, is significantly increased in platinum-resistant ovarian cell lines. Anti-annexin A3 immunostaining indicated that cancers from platinum-resistant patients also possess higher levels of annexin A3 than those from platinum-sensitive patients. Although expression of annexin A3 made susceptible ovarian cancer cells more resistant to platinum, expression of antisense annexin A3 downregulated its expression and rendered the resistant cells more sensitive to platinum. In athymic mice, the growth of tumors from inoculated SKOV3 cells was inhibited by the administration of platinum, whereas tumors from annexin A3-expressing SKOV3/Ann were resistant to platinum treatment. Interestingly, the intracellular platinum concentration and platinum-DNA binding are significantly lower in annexin A3-overexpressing cells than those in parental cells. The lower cisplatin concentration was also accompanied by reduced induction of p53, which could be restored by downregulation of annexin A3. These results indicate that increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. It seems to act by preventing uptake or accumulation of platinum in cells. Therefore, it is conceivable that annexin A3 could be a target for therapeutic intervention and may also serve as a biomarker for drug resistance in ovarian cancer patients. Cancer Res; 70(4); 1616-24. (C) 2010 AACR.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1158/0008-5472.can-09-3215
  3. View record in Web of Science®
  4. WOS: 000278485700036

Library Notes

  1. Fiscal Year: FY2009-2010
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel