Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells

Iwai Baba, Senji Shirasawa, Ryo Iwamoto, Koji Okumura, Toshiyuki Tsunoda, Miharu Nishioka, Kayako Fukuyama, Ken Yamamoto, Eisuke Mekada, Takehiko Sasazuki

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Abstract

To identify the genes located downstream of the activated Ki-Ras signaling pathways in human colon cancer cells, a PCR-based cDNA subtraction library was constructed between HCT116 cells and HCT116-derived activated Ki-ras-disrupted cells (HKe3). One of the genes in HCTll6 that was evidently up-regulated was epiregulin, a member of the epidermal growth factor family that is expressed in many kinds of human cancer cells. HKe3-stable transfectants expressing activated Ki-Ras regained over-expression of epiregulin. To further elucidate the biochemical structure and significance of epiregulin expression in tumorigenesis, HKe3-stable transfectants expressing epiregulin (e3-pSE cells) were established. Epiregulin existed as highly glycosylated membrane-bound forms, and TPA rapidly induced ectodomain shedding of epiregulin. Furthermore, the conditioned medium of e3-pSE cells showed more DNA synthesis for 32D cells expressing epidermal growth factor receptor (DER) cells than that of HKe3. Although anchorage-independent growth in soft agar was not observed for e3-pSE cells, tumorigenicity in nude mice was observed evidently, and their growth rate was correlated with each amount of exogenous epiregulin expression. These results suggested that activated Ki-Ras will be one of the factors contributing to the over-expression of epiregulin in human colon cancer cells, and that epiregulin will play a critical role in human tumorigenesis in vivo.

Original languageEnglish
Pages (from-to)6886-6889
Number of pages4
JournalCancer Research
Volume60
Issue number24
Publication statusPublished - Dec 15 2000

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Baba, I., Shirasawa, S., Iwamoto, R., Okumura, K., Tsunoda, T., Nishioka, M., Fukuyama, K., Yamamoto, K., Mekada, E., & Sasazuki, T. (2000). Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells. Cancer Research, 60(24), 6886-6889.