Limits...
Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer.

Li J, Ng EK, Ng YP, Wong CY, Yu J, Jin H, Cheng VY, Go MY, Cheung PK, Ebert MP, Tong J, To KF, Chan FK, Sung JJ, Ip NY, Leung WK - Br. J. Cancer (2009)

Bottom Line: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001).In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia.Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest.

View Article: PubMed Central - PubMed

Affiliation: Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT

Background: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis.

Methods: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro.

Results: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar.

Conclusion: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.

Show MeSH

Related in: MedlinePlus

Schematic diagram for the mechanisms of RAMP function in gastric cancer cells. Knockdown of RAMP inhibited gastric cancer cells growth, which was associated with several biological effects: (1) increasing the expression of cleaved caspase-9, caspase-3 and PARP, which in turn induced apoptosis; (2) inducing apoptosis caused by knockdown of RAMP was dependent on p53 and p21 pathways; (3) suppressing cell proliferation; (4) causing cell arrest in G2/M phase. On the other hand, overexpression of RAMP promoted growth capacity. Thus, RAMP may function as a novel oncogene in gastric cancer.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2736823&req=5

fig6: Schematic diagram for the mechanisms of RAMP function in gastric cancer cells. Knockdown of RAMP inhibited gastric cancer cells growth, which was associated with several biological effects: (1) increasing the expression of cleaved caspase-9, caspase-3 and PARP, which in turn induced apoptosis; (2) inducing apoptosis caused by knockdown of RAMP was dependent on p53 and p21 pathways; (3) suppressing cell proliferation; (4) causing cell arrest in G2/M phase. On the other hand, overexpression of RAMP promoted growth capacity. Thus, RAMP may function as a novel oncogene in gastric cancer.

Mentions: Upregulation of RAMP in gastric cancer cells and primary gastric cancer tissues prompted us to elucidate the role of RAMP in gastric cancer. We therefore analysed the effects of knocking down RAMP expression in two human gastric cancer cell lines. Knockdown of RAMP by siRNAs inhibited cell proliferation and anchorage-independent growth in soft agar in gastric cancer cells (Figure 6). In accordance with our findings, other reports indicated that RAMP plays a crucial role in cell survival, and complete loss of RAMP is lethal in early mouse embryonic development (Liu et al, 2007).


Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer.

Li J, Ng EK, Ng YP, Wong CY, Yu J, Jin H, Cheng VY, Go MY, Cheung PK, Ebert MP, Tong J, To KF, Chan FK, Sung JJ, Ip NY, Leung WK - Br. J. Cancer (2009)

Schematic diagram for the mechanisms of RAMP function in gastric cancer cells. Knockdown of RAMP inhibited gastric cancer cells growth, which was associated with several biological effects: (1) increasing the expression of cleaved caspase-9, caspase-3 and PARP, which in turn induced apoptosis; (2) inducing apoptosis caused by knockdown of RAMP was dependent on p53 and p21 pathways; (3) suppressing cell proliferation; (4) causing cell arrest in G2/M phase. On the other hand, overexpression of RAMP promoted growth capacity. Thus, RAMP may function as a novel oncogene in gastric cancer.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2736823&req=5

fig6: Schematic diagram for the mechanisms of RAMP function in gastric cancer cells. Knockdown of RAMP inhibited gastric cancer cells growth, which was associated with several biological effects: (1) increasing the expression of cleaved caspase-9, caspase-3 and PARP, which in turn induced apoptosis; (2) inducing apoptosis caused by knockdown of RAMP was dependent on p53 and p21 pathways; (3) suppressing cell proliferation; (4) causing cell arrest in G2/M phase. On the other hand, overexpression of RAMP promoted growth capacity. Thus, RAMP may function as a novel oncogene in gastric cancer.
Mentions: Upregulation of RAMP in gastric cancer cells and primary gastric cancer tissues prompted us to elucidate the role of RAMP in gastric cancer. We therefore analysed the effects of knocking down RAMP expression in two human gastric cancer cell lines. Knockdown of RAMP by siRNAs inhibited cell proliferation and anchorage-independent growth in soft agar in gastric cancer cells (Figure 6). In accordance with our findings, other reports indicated that RAMP plays a crucial role in cell survival, and complete loss of RAMP is lethal in early mouse embryonic development (Liu et al, 2007).

Bottom Line: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001).In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia.Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest.

View Article: PubMed Central - PubMed

Affiliation: Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT

Background: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis.

Methods: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro.

Results: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar.

Conclusion: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.

Show MeSH
Related in: MedlinePlus