Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma

Jm, Bhatavdekar; Patel, Devendra D.; Ghosh, Nandita; Chikhlikar, Priya R.; Trivedi, Trupti; Suthar, Tejal P.; Doctor, Sonali S.; Shah, Neelam G.; Balar, Damodar B.

doi:10.1007/bf02055433

Cited by 64 publications

(39 citation statements)

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“…Positive staining for c-myc was found in 71% and 65% of patients, respectively, and was not associated with Dukes' stage or histological grade in either study (Miller et al, 1992;Bhatavdekar et al, 1997). A significantly better overall survival was observed in the 17 patients without c-myc staining, when compared with the 31 with positive staining in the smaller study (Bhatavdekar et al, 1997).…”

Section: C-mycmentioning

confidence: 78%

“…Immunohistochemical analysis of c-myc protein in colorectal tumours has been evaluated in two separate studies [n = 118, Dukes' A, 7; B, 35; C, 41; D, 35 (Miller et al, 1992) and n = 48, Dukes' B, 24; C, 24 (Bhatavdekar et al, 1997)]. Positive staining for c-myc was found in 71% and 65% of patients, respectively, and was not associated with Dukes' stage or histological grade in either study (Miller et al, 1992;Bhatavdekar et al, 1997).…”

Section: C-mycmentioning

confidence: 99%

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Tumour markers of prognosis in colorectal cancer

1998

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Section: C-mycmentioning

confidence: 78%

Section: C-mycmentioning

confidence: 99%

Tumour markers of prognosis in colorectal cancer

1998

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“…[28][29][30][31] For example, Bcl-2 expression was associated with favorable outcome in stage II colon cancer. Some studies showed either no correlation between Bcl-2 expression and survival, or that overexpression of Bcl-2 correlated with an unfavorable outcome in colorectal cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies showed either no correlation between Bcl-2 expression and survival, or that overexpression of Bcl-2 correlated with an unfavorable outcome in colorectal cancer patients. [28][29][30][31] The clinical utility is not yet verified. In this study, we provide novel evidence to demonstrate that the interaction of PXN with Bcl-2 promotes Bcl-2 protein stability via phosphorylation of PXN at S272 and Bcl-2 at S87 by pPXN-Y31/Y118-mediated PAK1 and ERK activation, and this Bcl-2 protein stability confers 5-FU resistance in cells and xenograft tumors.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer

Huang

Chang

et al. 2014

Cell Death Differ

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5-Fluorouracil (5-FU) is chemotherapeutic agent widely used for the treatment of colorectal cancer. Unfortunately, advanced colorectal cancer is often resistance to such chemotherapy and poor outcome. An adaptor protein paxillin (PXN) is phosphorylated at Y31/Y118 (pPXN-Y31/Y118) by Src contributes to cell mobility and Ser (S)272 of PXN in LD4 domain is important to the interaction between PXN and Bcl-2. We thus hypothesized that pPXN-Y31/Y118 may be required for Bcl-2 protein stability via PXN interacting with Bcl-2 to confer 5-FU resistance in colorectal cancer. Mechanistically, pPXN-S272 is phosphorylated through pPXN-Y31/Y118-mediated p21 protein-activated kinase 1 (PAK1) activation and pPXN-S272 is required for PXN to interact with Bcl-2. The interaction between PXN and Bcl-2 is essential for Bcl-2 protein stability through phosphorylation of Bcl-2 at S87 (pBcl-2-S87) by pPXN-Y31/ Y118-mediated ERK activation. An increase in Bcl-2 expression by PXN is responsible for resistance to 5-FU. The resistance to 5-FU can be abolished by inhibitor of Src and PAK1 or Bcl-2 antagonist in cell and animal models. Among patients, Bcl-2 expression is positively correlated with expression of PXN and pPXN-S272, respectively. Patients with high PXN/high Bcl-2 or high pPXN-S272/high Bcl-2 tumors are commonly to have an unfavorable response to 5-FU-based chemotherapy, compared with patients who have high PXN, high pPXN-S272 or high Bcl-2 tumors alone. Therefore, we suggest that Src, PAK1 or Bcl-2 inhibitor may potentially overcome the resistance of 5-FU-based chemotherapy and consequently to improve outcomes in patients with PXN/Bcl-2 and pPXN-S272/Bcl-2-positive tumors. Cell Death and Differentiation (2015) 22, 779-789; doi:10.1038/cdd.2014.170; published online 17 October 2014The incidence of colorectal cancer has markedly increased over the past two decades and became the third leading cancer death in Taiwan.1,2 Patients with colorectal cancer commonly receive 5-fluorouracil (5-FU)-based chemotherapy after surgical resection. 3 The 5-year survival of Dukes B patients is approximately 75%, indicating that~25% of Dukes B patients may potentially benefit from adjuvant chemotherapy. 4 However, the response rate of advancedstage patients to 5-FU-based chemotherapy was only 10-15%. 5 Therefore, there is an urgent need to establish therapeutic biomarkers and available clinical approaches to improve the response of colorectal patients who received 5-FU-based chemotherapy.Paxillin (PXN) has been shown to promote tumor aggressiveness, including that of colorectal cancer. 6 A recent report indicated that PXN may promote cell proliferation in SW480 colon cancer cells and PXN expression was associated with overall survival (OS) but not related with Bcl-2 in colorectal cancer patients. 7 Our previous report indicated that phosphorylation of PXN at Y31/Y118 (pPXN-Y31/Y118) by Src signaling pathway increased Bcl-2 expression at a transcriptional level in lung cancer cells via ERK activation.8 Surprisingly, our preliminary data showed that ...

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“…Some authors (3) had demonstrated that bcl-2 overexpression seems to be associated with advanced histological grade, resulting in a more aggressive tumour. Others (2,4,9,14,24) had showed that patients with bcl-2 positive colorectal carcinoma had a more favourable clinical course.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 expression in rectal cancer

Contu

Moreira

2006

Arq. Gastroenterol.

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-Background -Proteins involved in apoptosis process seem to play an important role in colorectal carcinogenesis.Aim -To determine the prevalence of bcl-2 protein immunohistochemical expression and its relation with clinical and histopathological variables of rectal adenocarcinoma. Patients and methods -One hundred and thirty-two patients operated at "Hospital de Clínicas de Porto Alegre", Porto Alegre, RS, Brazil, between 1988 and 1999 were studied through immunohistochemical reaction using a monoclonal antibody anti-bcl-2 on formalin-fi xed, paraffi n-embedded tissue samples.Results -The prevalence of bcl-2 protein was 29.5%. There was a signifi cant increased number of positive bcl-2 cases among women as compared to men. There was no signifi cant association between bcl-2 and age, tumour site, histological grade, mucin production, depth of invasion, lymphatic involvement, distant metastasis or stage, despite a trend showing decreased immunoreactivity to bcl-2 among poorly and moderately differentiated tumours, as well as disseminated disease.Conclusions -Analysis of bcl-2 protein expression in tumour tissues, as well as other oncoproteins, may have a role in predict therapeutic response and prognosis of colorectal cancer. However, the potential use of bcl-2 protein assessment in the clinical set for management of rectal cancer remains to be determined.

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Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma

Abstract: These findings suggest that oncoprotein coexpression possesses significant prognostic and potential therapeutic value; incorporation of molecular markers into future prospective randomized trials is advisable.

Cited by 64 publications

References 17 publications

Tumour markers of prognosis in colorectal cancer

Tumour markers of prognosis in colorectal cancer

Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer

Bcl-2 expression in rectal cancer

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