Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms

Eisaku Kondo, Takayoshi Miyake, Masao Shibata, Toshikazu Kimura, Hiromi Iwagaki, Shin Ichi Nakamura, Takehiro Tanaka, Nobuya Ohara, Koichi Ichimura, Takashi Oka, Hiroyuki Yanai, Futoshi Shibasaki, Tadashi Yoshino

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)7255-7263
Number of pages9
JournalClinical Cancer Research
Volume11
Issue number20
DOIs
Publication statusPublished - Oct 15 2005

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Colorectal Neoplasms
Adenoma
Neoplasms
Adenocarcinoma
Ki-67 Antigen
Paraffin
Carcinogenesis
Research Design
Lymph Nodes
Phosphorylation
Apoptosis
Neoplasm Metastasis
Antigens
Survival
Antibodies

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 journalArticle

Kondo, E, Miyake, T, Shibata, M, Kimura, T, Iwagaki, H, Nakamura, SI, Tanaka, T, Ohara, N, Ichimura, K, Oka, T, Yanai, H, Shibasaki, F & Yoshino, T 2005, 'Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms', Clinical Cancer Research, vol. 11, no. 20, pp. 7255-7263. https://doi.org/10.1158/1078-0432.CCR-05-0274
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. / Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 20. pp. 7255-7263.
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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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