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Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer.

Shi J, Liu W, Sui F, Lu R, He Q, Yang Q, Lv H, Shi B, Hou P - Oncotarget (2015)

Bottom Line: Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors.Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects.AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.

ABSTRACT
Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors. It acts as a major oncogene in diverse cancers, whereas biological function of AIB1 in gastric cancer remains largely unclear. This study was designed to explore the role of AIB1 in gastric tumorigenesis and its potential as a useful prognostic marker and therapeutic target in this cancer. Our data demonstrated that AIB1 was significantly up-regulated in gastric cancer tissues as compared with control subjects. Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects. AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival. AIB1 knockdown in gastric cancer cells dramatically inhibited cell proliferation, invasiveness and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Mechanically, AIB1 promotes gastric cancer cell proliferation, survival and invasiveness through modulating major signaling pathways such as ErbB and Wnt/β-catenin pathways. Collectively, these findings suggest that AIB1 plays an important role in the pathogenesis of gastric cancer and represents a potential prognostic marker and therapeutic target for this cancer.

No MeSH data available.


Related in: MedlinePlus

Inhibition of gastric cancer cell migration and invasion by AIB1 down-regulationA. Cells transfected with si-AIB1-709 or si-NC were starved overnight and then seeded in the transwell chambers without matrigel for migration assay, and coated with matrigel for invasion assay, respectively. After a 24 h-culture, non-migrating (or non-invading) cells in the upper chamber were removed and migrating (or invading) cells were stained and calculated in five microscopic fields per sample. Shown are representative images of migrating (or invading) cells (left panels). Histograms (right panels), corresponding to left panels, show means ± SE of the numbers of migrating (or invading) cells from three independent assays. ***P < 0.001. B. qRT-PCR assay was performed to investigate the effect of AIB1 knockdown on the expression of metastasis-related genes MMP-2, -7, -9 and -14 in gastric cancer cells. Expression levels of these genes were normalized with 18S rRNA levels. Data were presented as mean ± SE. *P < 0.05; **P < 0.01; ***P < 0.001.
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Figure 4: Inhibition of gastric cancer cell migration and invasion by AIB1 down-regulationA. Cells transfected with si-AIB1-709 or si-NC were starved overnight and then seeded in the transwell chambers without matrigel for migration assay, and coated with matrigel for invasion assay, respectively. After a 24 h-culture, non-migrating (or non-invading) cells in the upper chamber were removed and migrating (or invading) cells were stained and calculated in five microscopic fields per sample. Shown are representative images of migrating (or invading) cells (left panels). Histograms (right panels), corresponding to left panels, show means ± SE of the numbers of migrating (or invading) cells from three independent assays. ***P < 0.001. B. qRT-PCR assay was performed to investigate the effect of AIB1 knockdown on the expression of metastasis-related genes MMP-2, -7, -9 and -14 in gastric cancer cells. Expression levels of these genes were normalized with 18S rRNA levels. Data were presented as mean ± SE. *P < 0.05; **P < 0.01; ***P < 0.001.

Mentions: Given that metastasis is the main cause of cancer-related death and AIB1 has been demonstrated to be involved in cancer metastasis [15, 28, 29], we thus attempted to investigate the effect of AIB1 down-regulation on the migration and invasion abilities of gastric cancer cells in this study. As shown in Fig. 4A, there were a significantly lower number of migrated cells in si-AIB1 transfected cells than in si-NC transfected cells. Moreover, the invasion assay showed that AIB1 knockdown significantly decreased the ability of cells to pass through the Matrigel-coated membrane. These results suggest that AIB1 knockdown significantly inhibits the migration and invasive potential of gastric cancer cells. Given a critical role of matrix metalloproteinases (MMPs) in cell migration and invasion [30], we next tested the effect of AIB1 down-regulation on the expression of MMP-2, -7, -9 and -14 genes in gastric cancer cells. As expected, AIB1 knockdown significantly inhibited the expression of these genes in at least two cell lines (Fig. 4B), suggesting that decrease in the metastasis-associated phenotypes may be link to the inhibition of MMPs in gastric cancer.


Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer.

Shi J, Liu W, Sui F, Lu R, He Q, Yang Q, Lv H, Shi B, Hou P - Oncotarget (2015)

Inhibition of gastric cancer cell migration and invasion by AIB1 down-regulationA. Cells transfected with si-AIB1-709 or si-NC were starved overnight and then seeded in the transwell chambers without matrigel for migration assay, and coated with matrigel for invasion assay, respectively. After a 24 h-culture, non-migrating (or non-invading) cells in the upper chamber were removed and migrating (or invading) cells were stained and calculated in five microscopic fields per sample. Shown are representative images of migrating (or invading) cells (left panels). Histograms (right panels), corresponding to left panels, show means ± SE of the numbers of migrating (or invading) cells from three independent assays. ***P < 0.001. B. qRT-PCR assay was performed to investigate the effect of AIB1 knockdown on the expression of metastasis-related genes MMP-2, -7, -9 and -14 in gastric cancer cells. Expression levels of these genes were normalized with 18S rRNA levels. Data were presented as mean ± SE. *P < 0.05; **P < 0.01; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4546471&req=5

Figure 4: Inhibition of gastric cancer cell migration and invasion by AIB1 down-regulationA. Cells transfected with si-AIB1-709 or si-NC were starved overnight and then seeded in the transwell chambers without matrigel for migration assay, and coated with matrigel for invasion assay, respectively. After a 24 h-culture, non-migrating (or non-invading) cells in the upper chamber were removed and migrating (or invading) cells were stained and calculated in five microscopic fields per sample. Shown are representative images of migrating (or invading) cells (left panels). Histograms (right panels), corresponding to left panels, show means ± SE of the numbers of migrating (or invading) cells from three independent assays. ***P < 0.001. B. qRT-PCR assay was performed to investigate the effect of AIB1 knockdown on the expression of metastasis-related genes MMP-2, -7, -9 and -14 in gastric cancer cells. Expression levels of these genes were normalized with 18S rRNA levels. Data were presented as mean ± SE. *P < 0.05; **P < 0.01; ***P < 0.001.
Mentions: Given that metastasis is the main cause of cancer-related death and AIB1 has been demonstrated to be involved in cancer metastasis [15, 28, 29], we thus attempted to investigate the effect of AIB1 down-regulation on the migration and invasion abilities of gastric cancer cells in this study. As shown in Fig. 4A, there were a significantly lower number of migrated cells in si-AIB1 transfected cells than in si-NC transfected cells. Moreover, the invasion assay showed that AIB1 knockdown significantly decreased the ability of cells to pass through the Matrigel-coated membrane. These results suggest that AIB1 knockdown significantly inhibits the migration and invasive potential of gastric cancer cells. Given a critical role of matrix metalloproteinases (MMPs) in cell migration and invasion [30], we next tested the effect of AIB1 down-regulation on the expression of MMP-2, -7, -9 and -14 genes in gastric cancer cells. As expected, AIB1 knockdown significantly inhibited the expression of these genes in at least two cell lines (Fig. 4B), suggesting that decrease in the metastasis-associated phenotypes may be link to the inhibition of MMPs in gastric cancer.

Bottom Line: Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors.Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects.AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.

ABSTRACT
Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors. It acts as a major oncogene in diverse cancers, whereas biological function of AIB1 in gastric cancer remains largely unclear. This study was designed to explore the role of AIB1 in gastric tumorigenesis and its potential as a useful prognostic marker and therapeutic target in this cancer. Our data demonstrated that AIB1 was significantly up-regulated in gastric cancer tissues as compared with control subjects. Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects. AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival. AIB1 knockdown in gastric cancer cells dramatically inhibited cell proliferation, invasiveness and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Mechanically, AIB1 promotes gastric cancer cell proliferation, survival and invasiveness through modulating major signaling pathways such as ErbB and Wnt/β-catenin pathways. Collectively, these findings suggest that AIB1 plays an important role in the pathogenesis of gastric cancer and represents a potential prognostic marker and therapeutic target for this cancer.

No MeSH data available.


Related in: MedlinePlus