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Loss of p16 INK4a expression is associated with vascular endothelial growth factor expression in squamous cell carcinoma of the esophagus
Vascular endothelial growth factor (VEGF) expression has been suggested to correlate with intratumoral microvessel density, tumor advancement and prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies have showed that disruption of cell cycle regulator p16 is related to oncogenesis...
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Published in: | International journal of cancer 2004-04, Vol.109 (4), p.483-490 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Vascular endothelial growth factor (VEGF) expression has been suggested to correlate with intratumoral microvessel density, tumor advancement and prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies have showed that disruption of cell cycle regulator p16 is related to oncogenesis and tumor progression in ESCC. We hypothesized that VEGF expression in ESCC is reflected by abnormalities in the
p16
INK4a
gene. To clarify the regulatory role of
p16
INK4a
in VEGF expression
in vitro
, we transferred the
p16
INK4a
gene into a
p16
INK4a
‐deleted ESCC cell line and observed changes in VEGF expression. Furthermore, we immunohistochemically assessed the expression of the cell cycle regulators (p16, p53 and RB) and VEGF in 90 surgically resected specimens of ESCC. Introduction of
p16
INK4a
cDNA by the p16 expression vector significantly suppressed cell proliferation in the
p16
INK4a
‐deleted cell line TE8 (
p
< 0.0001). VEGF secretion by TE8 cells transfected with the
p16
INK4a
vector was significantly suppressed as compared to non‐transfected TE8 cells (
p
< 0.0001) and TE8 cells transfected with a control vector (
p
= 0.0015). The immunohistochemical studies of ESCC primary tumor specimens showed that loss of p16 expression was significantly correlated with VEGF‐positive expression (
p
= 0.0004). The cumulative postoperative survival rate in the group with p16‐positive and VEGF‐negative expression was significantly higher than in the other groups. Neither p53 nor RB expression had any impact on outcome. Aberrant p53 expression tended to be associated with VEGF expression, but the trend did not reach statistical significance. Our study demonstrated that VEGF expression was correlated with p16 expression in ESCC. Our results suggest that p16 may have a regulatory role in VEGF expression in ESCC. © 2004 Wiley‐Liss, Inc. |
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ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.11734 |