Abstract
The aim is to investigate the clinical implications of the Oct-4 and Nestin protein in human breast cancers. A total of 346 cases including 26 fresh and 320 paraffin-embedded tumor tissues were selected for characterizing the frequency of CD44+CD24− tumor cells by flow cytometry and the differential expression of the stem cell-related genes between CD44+CD24− and non-CD44+CD24− tumor cells was analyzed by PCR Array and immunofluorescence. In comparison with the non-CD44+CD24− tumor cells, the CD44+CD24−, particularly for those with high percentage of Oct-4+ and Nestin+, tumor cells had higher tumorigenicity by forming mammospheres in vitro. More importantly, 42 (13.125%) out of 320 tumor tissues were positive for Oct-4 and Nestin staining. Universal analysis and multivariate analysis revealed that the expression of Oct-4 and Nestin was associated significantly with younger age, pathogenic degrees, lymph node metastasis and triple-negative breast cancer independently (P < 0.05) as well as shorter survival (P = 0.001). Oct-4 and Nestin were important regulators of the development of breast cancer, and Oct-4 and Nestin may be used as predictors for the prognosis of breast cancers.
Similar content being viewed by others
References
Zorzi M, Guzzinati S, Puliti D, Paci E (2010) A simple method to estimate the episode and programme sensitivity of breast cancer screening programmes. J Med Screen 17:132–138
Dowling EC, Klabunde C, Patnick J, Ballard-Barbash R; for the International Cancer Screening Network (ICSN) (2010) Breast and cervical cancer screening programme implementation in 16 countries. J Med Screen 17:139–146
Faghih Z, Erfani N, Razmkhah M, Sameni S, Talei A, Ghaderi A (2009) Interleukin13 haplotypes and susceptibility of Iranian women to breast cancer. Mol Biol Rep 36(7):1923–1928
Akisik E, Yazici H, Dalay N (2011) ARLTS1, MDM2 and RAD51 gene variations are associated with familial breast cancer. Mol Biol Rep 38(1):343–348
Fabrizi E, di Martino S, Pelacchi F, Ricci-Vitiani L (2010) Therapeutic implications of colon cancer stem cells. World J Gastroenterol 16:3871–3877
Ginestier C, Charafe-Jauffret E, Birnbaum D (2010) Targeting breast cancer stem cells: fishing season open! Breast Cancer Res 12:312
Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF (2007) The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 356:217–226
Monsef N, Soller M, Isaksson M, Abrahamsson PA, Panagopoulos I (2009) The expression of pluripotency marker Oct 3/4 in prostate cancer and benign prostate hyperplasia. Prostate 69:909–916
Park D, Xiang AP, Mao FF, Zhang L, Di CG, Liu XM, Shao Y, Ma BF, Lee JH, Ha KS, Walton N, Lahn BT (2010) Nestin is required for the proper self-renewal of neural stem cells. Stem Cells 28:2162–2171
Liu C, Chen B, Zhu J, Zhang R, Yao F, Jin F, Xu H, Lu P (2010) Clinical implications for nestin protein expression in breast cancer. Cancer Sci 101:815–819
Liu CG, Lu Y, Wang BB, Zhang YJ, Zhang RS, Lu Y, Chen B, Xu H, Jin F, Lu P (2011) Clinical implications of stem cell gene oct-4 expression in breast cancer. Ann Surg 253(6):1165–1171
Grimshaw MJ, Cooper L, Papazisis K, Coleman JA, Bohnenkamp HR, Chiapero-Stanke L, Taylor-Papadimitriou J, Burchell JM (2008) Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells. Breast Cancer Res 10:R52
Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE (2005) Oct-4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502
Naik RP, Jin D, Chuang E, Gold EG, Tousimis EA, Moore AL, Christos PJ, de Dalmas T, Donovan D, Rafii S, Vahdat LT (2008) Circulating endothelial progenitor cells correlate to stage in patients with invasive breast cancer. Breast Cancer Res Treat 107:133–138
Guo J, Zhou J, Ying X, Men Y, Li RJ, Zhang Y, Du J, Tian W, Yao HJ, Wang XX, Ju RJ, Lu WL (2010) Effects of stealth liposomal daunorubicin plus tamoxifen on the breast cancer and cancer stem cells. J Pharm Pharm Sci 13:136–151
Li H, Cherukuri P, Li N, Cowling V, Spinella M, Cole M, Godwin AK, Wells W, DiRenzo J (2007) Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. Cancer Res 67:501–510
Acknowledgment
This study was supported by the grant from the China National Natural Science Foundation (No. 81102029 and 81172047).
Conflict of interests
The authors stated no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Caigang Liu and Xuezhao Cao were co-first authors.
Rights and permissions
About this article
Cite this article
Liu, C., Cao, X., Zhang, Y. et al. Co-expression of Oct-4 and Nestin in human breast cancers. Mol Biol Rep 39, 5875–5881 (2012). https://doi.org/10.1007/s11033-011-1398-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-011-1398-6