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Open Access Research article

G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells

Chang-Chieh Wu1, Fu-Ming Tsai2, Rong-Yaun Shyu34, Ya-Ming Tsai2, Chun-Hua Wang5 and Shun-Yuan Jiang2*

Author Affiliations

1 Department of Surgery, Tri-Service General Hospital, 325 Chengung Rd, Sec 2, Taipei, 114 Taiwan

2 Department of Research, Buddhist Tzu Chi General Hospital Taipei Branch, 289 Jianguo Rd, Sindian District, New Taipei City, 231 Taiwan

3 Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, 289 Jianguo Rd, Sindian District, New Taipei City, 231 Taiwan

4 School of Medicine, Tzu Chi University, 701 Zhongyang Rd, Sec 3, Hualien, 970 Taiwan

5 Department of Dermatology, Buddhist Tzu Chi General Hospital Taipei Branch, 289 Jianguo Rd, Sindian District, New Taipei City, 231 Taiwan

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BMC Cancer 2011, 11:175  doi:10.1186/1471-2407-11-175

Published: 17 May 2011

Abstract

Background

Tazarotene-induced gene 1 (TIG1) is a retinoid-inducible type II tumour suppressor gene. The B isoform of TIG1 (TIG1B) inhibits growth and invasion of cancer cells. Expression of TIG1B is frequently downregulated in various cancer tissues; however, the expression and activities of the TIG1A isoform are yet to be reported. Therefore, this study investigated the effects of the TIG1A and TIG1B isoforms on cell growth and gene expression profiles using colon cancer cells.

Methods

TIG1A and TIG1B stable clones derived from HCT116 and SW620 colon cancer cells were established using the GeneSwitch system; TIG1 isoform expression was induced by mifepristone treatment. Cell growth was assessed using the WST-1 cell proliferation and colony formation assays. RNA interference was used to examine the TIG1 mediating changes in cell growth. Gene expression profiles were determined using microarray and validated using real-time polymerase chain reaction, and Western blot analyses.

Results

Both TIG1 isoforms were expressed at high levels in normal prostate and colon tissues and were downregulated in colon cancer cell lines. Both TIG1 isoforms significantly inhibited the growth of transiently transfected HCT116 cells and stably expressing TIG1A and TIG1B HCT116 and SW620 cells. Expression of 129 and 55 genes was altered upon induction of TIG1A and TIG1B expression, respectively, in stably expressing HCT116 cells. Of the genes analysed, 23 and 6 genes were upregulated and downregulated, respectively, in both TIG1A and TIG1B expressing cells. Upregulation of the G-protein-coupled receptor kinase 5 (GRK5) was confirmed using real-time polymerase chain reaction and Western blot analyses in both TIG1 stable cell lines. Silencing of TIG1A or GRK5 expression significantly decreased TIG1A-mediated cell growth suppression.

Conclusions

Expression of both TIG1 isoforms was observed in normal prostate and colon tissues and was downregulated in colon cancer cell lines. Both TIG1 isoforms suppressed cell growth and stimulated GRK5 expression in HCT116 and SW620 cells. Knockdown of GRK5 expression alleviated TIG1A-induced growth suppression of HCT116 cells, suggesting that GRK5 mediates cell growth suppression by TIG1A. Thus, TIG1 may participate in the downregulation of G-protein coupled signaling by upregulating GRK5 expression.

Keywords:
RARRES1; TIG1; GRK5; microarray; colon cancer cells; tumour suppressor