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

Research output: Contribution to journalArticle

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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

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Colonic Neoplasms
Carcinogenesis
HCT116 Cells
Epiregulin
Conditioned Culture Medium
Growth
Gene Library
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Nude Mice
Genes
Agar
Polymerase Chain Reaction
Membranes
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Baba, I., Shirasawa, S., Iwamoto, R., Okumura, K., Tsunoda, T., Nishioka, M., ... 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.

Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells. / Baba, Iwai; Shirasawa, Senji; Iwamoto, Ryo; Okumura, Koji; Tsunoda, Toshiyuki; Nishioka, Miharu; Fukuyama, Kayako; Yamamoto, Ken; Mekada, Eisuke; Sasazuki, Takehiko.

In: Cancer Research, Vol. 60, No. 24, 15.12.2000, p. 6886-6889.

Research output: Contribution to journalArticle

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, vol. 60, no. 24, pp. 6886-6889.
Baba, Iwai ; Shirasawa, Senji ; Iwamoto, Ryo ; Okumura, Koji ; Tsunoda, Toshiyuki ; Nishioka, Miharu ; Fukuyama, Kayako ; Yamamoto, Ken ; Mekada, Eisuke ; Sasazuki, Takehiko. / Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells. In: Cancer Research. 2000 ; Vol. 60, No. 24. pp. 6886-6889.
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