| | |  | | | | Record from Web of Science® | | | | | | |
| The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers |
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| Author(s): Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N, Liu JS, Smith-McCune K, Lu KH, Fishman D, Gray JW, Mills GB |
| Source: NATURE MEDICINE Volume: 10 Issue: 11 Pages: 1251-1256 Published: NOV 2004 |
| Times Cited: 93 References: 29 |
| Abstract: High-density array comparative genomic hybridization (CGH)(1) showed amplification of chromosome 1q22 centered on the RAB25 small GTPase(2), which is implicated in apical vesicle trafficking(3), in approximately half of ovarian and breast cancers. RAB25 mRNA levels were selectively increased in stage III and IV serous epithelial ovarian cancers compared to other genes within the amplified region, implicating RAB25 as a driving event in the development of the amplicon. Increased DNA copy number or RNA level of RAB25 was associated with markedly decreased disease-free survival or overall survival in ovarian and breast cancers, respectively. Forced expression of RAB25 markedly increased anchorage-dependent and anchorage-independent cell proliferation, prevented apoptosis and anoikis, including that induced by chemotherapy, and increased aggressiveness of cancer cells in vivo. The inhibition of apoptosis was associated with a decrease in expression of the proapoptotic molecules, BAK and BAX, and activation of the antiapoptotic phosphatidylinositol 3 kinase (PI3K) and AKT pathway, providing potential mechanisms for the effects of RAB25 on tumor aggressiveness. Overall, these studies implicate RAB25, and thus the RAB family of small G proteins, in aggressiveness of epithelial cancers. |
| Document Type: Article |
| Language: English |
| Reprint Address: Mills, GB (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77054 USA |
Addresses:
1. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77054 USA
2. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA
3. Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC V6H 3V5 Canada
4. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
5. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA
6. Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA
7. NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: 866PR |
| ISSN: 1078-8956 |
| DOI: 10.1038/nm1125 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |