Abstract
Our aim for this study was to investigate the correlation and clinical significance between the expression of IGF-II and Bcl-2 in colorectal adenocarcinoma, especially in terms of the metastasis of colorectal adenocarcinoma. Sixty paraffin embedded samples of colorectal adenocarcinoma were selected, and fifteen normal colorectal tissues were used as controls. IGF-II mRNA was detected using in situ hybridization, and the expression of Bcl-2 along with the proliferating cell nuclear antigen (PCNA) protein was detected through immunohistochemistry. The TUNEL assay was used to detect apoptosis. Specimens with a positive cell ratio less than 30% were defined as negative. The levels of IGF-II mRNA and the Bcl-2 protein were significantly higher in colorectal adenocarcinoma (39.64 ± 7.38% and 30.74 ± 7.22%, respectively) than in normal colorectal tissues (22.56 ± 4.21% and 12.17 ± 1.94%, respectively) (P < 0.01). The levels were related to Dukes′ stage and lymph node metastases, but were unrelated to patient age, gender, tumor site, tumor size, and tumor differentiation. Also, a negative correlation was observed between IGF-II mRNA and Bcl-2 protein (P < 0.05) during Dukes′ stages. In addition, a positive correlation between IGF-II mRNA and PCNA or apoptosis, as well as a negative correlation between Bcl-2 and apoptosis were observed (P < 0.01). There was no correlation between Bcl-2 and PCNA (P > 0.05). The patients detected as IGF-II mRNA (+) and Bcl-2 (−) showed the worst prognosis. The expression of IGF-II and Bcl-2 was correlated with the clinical manifestation of colorectal adenocarcinoma; thus, the assessment of both IGF-II and Bcl-2’s status will provide important information regarding the diagnosis and prognosis of colorectal adenocarcinoma.
Similar content being viewed by others
References
Tang DQ. Modern oncology. 2nd ed. Shang Hai: The Press of Shang Hai Medical University; 2000 p. 121.
Lee AV, Darbre P, King RJ. Processing of insulin-like growth factor-II(IGF-II) by human breast cancer cells. Mol Cell Endocrinol. 1994;99:211–20.
Singh SK, Moretta D, Almaguel F, De León M, De León DD. Precursor IGF-II (proIGF-II) and mature IGF-II (mIGF-II) induce Bcl-2 and Bcl-X L expression through different signaling pathways in breast cancer cells. Growth Factors. 2008;26:92–103.
Cariani E, et al. Differential expression of insulin-like growth factor-IImRNA in human primary liver cancers, benign liver tumors, and liver cirrhosis. Cancer Res. 1988;48:6844–9.
Kalla Singh S, et al. Differential insulin-like growth factor II (IGF-II) expression: a potential role for breast cancer survival disparity. Growth Horm IGF Res. 2010;20:162–70.
Höppener JW, et al. Expression of insulin-like growth factor-I and -II renes in human smooth muscle tumors. EMBO J. 1988;7:1379–85.
Tricoli JV, et al. Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res. 1986;46:6169–6173.
Macaulay VM. Insulin-like growth factors and cancer. Br J Cancer. 1992;65:311–20.
Peng NM, Wang ZL. The basis and clinic of cell apoptosis.1st ed. Beijing: The Press of People Health; 2000. p. 251–252.
Mohan S, Jennings JC, Linkhart TA, Baylink DJ. Primary structure of human skeletal growth factor: homology with human insulin-like growth factor-II. Biohim Biophys Acta. 1988;966:44–55.
Berger Abi. Insulin-like growth factor and cognitive function. BMJ. 2001; 322:203.
McKeithan TW, Rowley JD, Shows TB, Diaz MO. Cloning of the chromosome breakpoint of neoplastic B cells with the t (14, 18) chromosometranslocation. Science. 1984;226:1097–9.
Hockenbery D, Nuñez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990;384:334–6.
Freier S, et al. Expression of the insulin-like growth factors and their receptors in adenocarinoma of the colon. Gut. 1999;44:704–8.
Ishijima N, Miki C, Ishida T, Kinoshita T, Suzuki H. The Immunohistochemical expression of Bcl-2 oncoprotein in colorectal carcinoma. Surg Today. 1999;29:682–4.
Evertsson S, Bartik Z, Zhang H, Jansson A, Sun XF. Apoptosis in relation to proliferating cell nuclear antigen and Dukes′stage in colorectal adenocarcinoma. Int J Oncol. 1999;15:53–8.
Zheng E. Mechanism of carcinoma. 1st ed. Beijing: The Press of BeiJing; 1999. p. 189–194.
Rohlik QT, Adams D, Kull FC Jr, Jacobs S. An antibody to the receptor for insulin-like growth factor I inhibits the growth of MCF-7 cells in tissue culture. Biochem Biophys Res Commun. 1987;149:276–81.
Huang GS, et al. Insulin-like growth factor 2 expression modulates Taxol resistance and is a candidate biomarker for reduced disease-free survival in ovarian cancer. Clin Cancer Res. 2010;16:2999–3010.
Hassan AB, Macaulay VM. The insulin-like growth factor system as a therapeutic target in colorectal cancer. Ann Oncol. 2002;13:349–56.
Avnet S, et al. Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma. Cancer Res. 2009;69:2443–52.
Yang DH, et al. Inhibitory effect of IGF-II antisense RNA on malignant phenotype of hepatocellular carcinoma. World J Gastroenterol. 2000;6:266–7.
Kawamoto K, et al. Expression of insulin-like growth factor-IIcan predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival. Oncology. 1998;55:242–8.
Leahy DT, Mulcahy HE, O’Donoghue DP, Parfrey NA. Bcl-2 protein expression is associatated with better prognosis in colorectal cancer. Histopathology. 1999;35:360–7.
Acknowledgment
This work was supported in part by National Natural Science Foundation of China (NO. 30801369 and NO. 81001067).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Dr Ming-Sheng Zhang and Dr Yuan Chen contribute equally to this study.
Rights and permissions
About this article
Cite this article
Zhang, MS., Hu, AH., Qiu, H. et al. The correlation between IGF-II and Bcl-2 expression in colorectal adenocarcinoma. Med Oncol 29, 928–932 (2012). https://doi.org/10.1007/s12032-011-9881-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-011-9881-4