The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers

Speaker: 林純羽                                Time: 3/30/05

Commentator: 周楠華 教授                   Place: 601 Room

Abstract:

  Most cancers have chromosomal abnormalities in number and/or structure. For example, deletion and copy number increase contribute to the alterations in the expression of tumor suppressor genes and oncogenes, respectively. In addition, gene dosage variations may involve in cancer progressions. In this study, comparative genomic hybridization was first applied to detect the chromosomal aberrations of ovarian cancer. The authors identified an increase of copy number on chromosome 1q22, and then analyzed the expression of genes located within this region. Among them, elevated RNA level of RAB25 small GTPase (Ras-related protein Rab-25) was detected in most of ovarian cancers, and was tumor stage-dependent (P < 0.001). In ovarian cancer cohort, expression of RAB25 was inversely related to patient survival (P < 0.05). To elucidate the mechanisms of RAB25 involved in cancer progression, enforced expression of RAB25 was demonstrated to enhance the cell survival in vitro under multiple stress conditions, including chemotherapy, and the aggressiveness of ovarian cancer cells in vivo. Expression of RAB25 also inhibited the apoptosis associated with activation of PI3K/AKT pathway or reduced expression of BAK and BAX. However, RAB25 was not sufficient in transformation of ovarian epithelial cells, but can stimulate the growth of transformed cell lines. Taken together, RAB25 seems to implicate in the aggressiveness of ovarian cancer, and thus may have potential in predicting patient prognosis or be chosen as a novel therapeutic target.

References:

1.      Kwai Wa Cheng, John P Lahad1,Wen-lin Kuo, Anna Lapuk, Kyosuke Yamada, Nelly Auersperg, Jinsong Liu, Karen Smith-McCune, Karen H Lu, David Fishman, Joe W Gray & Gordon B Mills. 2004 . The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. NATURE MEDICINE 10:1251-1256.

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