Abstract
Purpose: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bct-2. Experimental Design: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. Results: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positively 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P <0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P <0.05) and correlated with clinical stages and lymph node metastasis (P <0.05 and P <0.05, respectively). Conclusions: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 7255-7263 |
| Number of pages | 9 |
| Journal | Clinical Cancer Research |
| Volume | 11 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - Oct 15 2005 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms. / Kondo, Eisaku; Miyake, Takayoshi; Shibata, Masao; Kimura, Toshikazu; Iwagaki, Hiromi; Nakamura, Shin Ichi; Tanaka, Takehiro; Ohara, Nobuya; Ichimura, Koichi; Oka, Takashi; Yanai, Hiroyuki; Shibasaki, Futoshi; Yoshino, Tadashi.
In: Clinical Cancer Research, Vol. 11, No. 20, 15.10.2005, p. 7255-7263.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms
AU - Kondo, Eisaku
AU - Miyake, Takayoshi
AU - Shibata, Masao
AU - Kimura, Toshikazu
AU - Iwagaki, Hiromi
AU - Nakamura, Shin Ichi
AU - Tanaka, Takehiro
AU - Ohara, Nobuya
AU - Ichimura, Koichi
AU - Oka, Takashi
AU - Yanai, Hiroyuki
AU - Shibasaki, Futoshi
AU - Yoshino, Tadashi
PY - 2005/10/15
Y1 - 2005/10/15
N2 - Purpose: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bct-2. Experimental Design: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. Results: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positively 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P <0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P <0.05) and correlated with clinical stages and lymph node metastasis (P <0.05 and P <0.05, respectively). Conclusions: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.
AB - Purpose: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bct-2. Experimental Design: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. Results: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positively 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P <0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P <0.05) and correlated with clinical stages and lymph node metastasis (P <0.05 and P <0.05, respectively). Conclusions: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.
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UR - http://www.scopus.com/inward/citedby.url?scp=27144515512&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-0274
DO - 10.1158/1078-0432.CCR-05-0274
M3 - Article
C2 - 16243795
AN - SCOPUS:27144515512
VL - 11
SP - 7255
EP - 7263
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 20
ER -