Expression and analysis of HIC-1 and HMMR in breast cancer

doi:10.16150/j.1671-2870.2017.01.014

Abstract

Abstract: Objective: To study the expression of tumor suppressor gene hypermethylated in cancer 1(HIC-1)and oncogene hyaluronan-mediated motility receptor (HMMR) in lobular hyperplasia of mammary gland, breast fibroadenoma and breast cancer, as well as their relationship with the clinicopathological parameters of breast cancer. Methods: Expressions of HIC-1 and HMMR was examined by immunohistochemistry on 57 resected tissue samples taken at breast surgery: lobular hyperplasia 17 cases, fibroadenoma 20 cases and breast cancer 20 cases. The staining results were assessed semi-quantitatively, and were analyzed with the clinicopathological parameters of breast cancer. Results: ① HIC-1 was mo-derately positive in lobular hyperplasia and fibroadenoma tissue (average score 5.65), and was weakly positive in breast cancer tissue(average score 2.15). The difference in expression of HIC-1 between mammary benign lesions and breast cancer was significant (P<0.001). ② Expression of HMMR in mammary benign lesions was low (average score of fibroadenoma was 0.3, average score of lobular hyperplasia was 0), while the expression of HMMR in breast cancer was with an average score of 2.3 (P<0.001). ③ No obvious correlation was observed between protein expression of HIC-1 and HMMR and cli-nicopathological parameters of breast cancer. Conclusions: Expression of tumor suppression gene HIC-1 is significantly low and oncogene HMMR is relatively high in breast cancer. HIC-1 and the downstream gene HMMR regulated by HIC-1 may be involved in the development and progress of breast cancer.

Key words: Breast cancer, Hypermethylated in cancer 1, Hyaluronan-mediated motility receptor, Immunohistochemis-try, Clinicopathology

CLC Number:

R737.9

WU Yan, DING Peifen, GU Yan, GUO Shanyu, DAI Qiancheng, ZHANG Wei. Expression and analysis of HIC-1 and HMMR in breast cancer[J]. Journal of Diagnostics Concepts & Practice, 2017, 16(01): 73-78.

References

[1] Fan L, Strasser-Weippl K, Li JJ, et al.Breast cancer in China[J]. Lancet Oncol,2014,15(7):e279-e289.
[2] Lu Y, Lin YZ, LaPushin R, et al. The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells[J]. Oncogene,1999,18(50):7034-7045.
[3] Fujii H, Biel MA, Zhou W, et al.Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer[J]. Oncogene,1998,16(16):2159-2164.
[4] Kanai Y, Hui AM, Sun L, et al.DNA hypermethylation at the D17S5 locus and reduced HIC-1 mRNA expression are associated with hepatocarcinogenesis[J]. Hepatology,1999,29(3):703-709.
[5] Nishida N, Nagasaka T, Nishimura T, et al.Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma[J]. Hepatology,2008,47(3):908-918.
[6] Misra S, Hascall VC, Markwald RR, et al.Interactions between hyaluronan and its receptors(CD44, RHAMM) regulate the activities of inflammation and cancer[J]. Front Immunol,2015,6:201.
[7] 刘雷, 郭磊, 王志威, 等. 新型标志物HAB18G/CD147在大样本胃癌组织中的表达研究[J]. 诊断理论与实践,2012, 11(1):42-46.
[8] 赵峰, 张伟. HIC-1基因在肿瘤发生发展中的作用[J]. 外科理论与实践,2012,17(5):501-504.
[9] Wales MM, Biel MA, el Deiry W, et al. p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3[J]. Nat Med,1995,1(6):570-577.
[10] Boulay G, Malaquin N, Loison I, et al.Loss of hypermethylated in cancer 1 (HIC1) in breast cancer cells contributes to stress-induced migration and invasion through β-2 adrenergic receptor (ADRB2) misregulation[J]. J Biol Chem,2012,287(8):5379-5389.
[11] Nicoll G, Crichton DN, McDowell HE, et al. Expression of the hypermethylated in cancer gene (HIC-1) is associa-ted with good outcome in human breast cancer[J]. Br J Cancer,2001,85(12):1878-1882.
[12] 赵峰, 顾岩, 郭善禹, 等. HIC-1基因在乳腺癌的表达及其对细胞增殖和凋亡的影响[J]. 外科理论与实践,2013, 18(2):159-164.
[13] Zhao F, Pan S, Gu Y, et al.Small activating RNA restores the activity of the tumor suppressor HIC-1 on breast cancer[J]. PLoS One,2014,9(1):e86486.
[14] Entschladen F, Drell TL 4th, Lang K, et al. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters[J]. Lancet Oncol,2004,5(4):254-258.
[15] Woodhouse EC, Chuaqui RF, Liotta LA.General mechanisms of metastasis[J]. Cancer,1997,80(8 Suppl):1529-1537.
[16] Wang C, Thor AD, Moore DH 2nd, et al. The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression[J]. Clin Cancer Res,1998,4(3):567-576.
[17] 程晓博, 范莹, 涂巍. CD168与乳腺癌预后的关系[J]. 辽宁大学学报,2013,40(2):185-188.
[18] 马万山, 李晓冰, 汪运山, 等. 胃癌患者原癌基因和抑癌基因的表达谱研究[J]. 肿瘤防治杂志,2002,9(4):379-381.