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Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis.

Publication ,  Journal Article
Patil, MA; Lee, SA; Macias, E; Lam, ET; Xu, C; Jones, KD; Ho, C; Rodriguez-Puebla, M; Chen, X
Published in: Cancer Res
January 1, 2009

Activation of c-Met signaling and beta-catenin mutations are frequent genetic events observed in liver cancer development. Recently, we demonstrated that activated beta-catenin can cooperate with c-Met to induce liver cancer formation in a mouse model. Cyclin D1 (CCND1) is an important cell cycle regulator that is considered to be a downstream target of beta-catenin. To determine the importance of CCND1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis, we investigated the genetic interactions between CCND1, beta-catenin, and c-Met in liver cancer development using mouse models. We coexpressed CCND1 with c-Met in mice and found CCND1 to cooperate with c-Met to promote liver cancer formation. Tumors induced by CCND1/c-Met had a longer latency period, formed at a lower frequency, and seemed to be more benign compared with those induced by beta-catenin/c-Met. In addition, when activated beta-catenin and c-Met were coinjected into CCND1-null mice, liver tumors developed despite the absence of CCND1. Intriguingly, we observed a moderate accelerated tumor growth and increased tumor malignancy in these CCND1-null mice. Molecular analysis showed an up-regulation of cyclin D2 (CCND2) expression in CCND1-null tumor samples, indicating that CCND2 may replace CCND1 in hepatic tumorigenesis. Together, our results suggest that CCND1 functions as a mediator of beta-catenin during HCC pathogenesis, although other molecules may be required to fully propagate beta-catenin signaling. Moreover, our data suggest that CCND1 expression is not essential for liver tumor development induced by c-Met and beta-catenin.

Duke Scholars

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

January 1, 2009

Volume

69

Issue

1

Start / End Page

253 / 261

Location

United States

Related Subject Headings

  • beta Catenin
  • Up-Regulation
  • Transfection
  • Proto-Oncogene Proteins c-met
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice
  • Male
  • Liver Neoplasms, Experimental
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Patil, M. A., Lee, S. A., Macias, E., Lam, E. T., Xu, C., Jones, K. D., … Chen, X. (2009). Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis. Cancer Res, 69(1), 253–261. https://doi.org/10.1158/0008-5472.CAN-08-2514
Patil, Mohini A., Susie A. Lee, Everardo Macias, Ernest T. Lam, Chuanrui Xu, Kirk D. Jones, Coral Ho, Marcelo Rodriguez-Puebla, and Xin Chen. “Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis.Cancer Res 69, no. 1 (January 1, 2009): 253–61. https://doi.org/10.1158/0008-5472.CAN-08-2514.
Patil MA, Lee SA, Macias E, Lam ET, Xu C, Jones KD, et al. Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis. Cancer Res. 2009 Jan 1;69(1):253–61.
Patil, Mohini A., et al. “Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis.Cancer Res, vol. 69, no. 1, Jan. 2009, pp. 253–61. Pubmed, doi:10.1158/0008-5472.CAN-08-2514.
Patil MA, Lee SA, Macias E, Lam ET, Xu C, Jones KD, Ho C, Rodriguez-Puebla M, Chen X. Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis. Cancer Res. 2009 Jan 1;69(1):253–261.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

January 1, 2009

Volume

69

Issue

1

Start / End Page

253 / 261

Location

United States

Related Subject Headings

  • beta Catenin
  • Up-Regulation
  • Transfection
  • Proto-Oncogene Proteins c-met
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice
  • Male
  • Liver Neoplasms, Experimental
  • Humans