Cyclin D1 expression is correlated with cell differentiation and cell proliferation in oral squamous cell carcinomas

Ohnishi,Yuichi; Watanabe,Masahiro; Wato,Masahiro; Tanaka,Akio; Kakudo,Kenji; Nozaki,Masami

doi:10.3892/ol.2014.1880

Cyclin D1 expression is correlated with cell differentiation and cell proliferation in oral squamous cell carcinomas

Authors:
- Yuichi Ohnishi
- Masahiro Watanabe
- Masahiro Wato
- Akio Tanaka
- Kenji Kakudo
- Masami Nozaki
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Affiliations: Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573‑1121, Japan, Department of Oral Pathology, Osaka Dental University, Hirakata, Osaka 573‑1121, Japan, Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565‑0871, Japan
Published online on: February 13, 2014 https://doi.org/10.3892/ol.2014.1880
Pages: 1123-1127

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Abstract

The present study conducted an immunohistochemical investigation of cyclin D1 and Ki‑67 expression in oral squamous cell carcinoma (SCC) to evaluate the correlations between cell differentiation, cell proliferation and metastasis, and the effect of anticancer drug medication and cyclin D1 expression. Cyclin D1 and Ki‑67 were detected clearly in the nuclei of 35 SCC samples. No correlation between cyclin D1 protein expression and oral SCC differentiation was found. By contrast, the majority of metastatic foci (90%) exhibited strong cyclin D1 expression, whereas weak expression was observed in metastatic foci with pre‑operative adjuvant therapy. Additionally, cyclin D1 and Ki‑67 were expressed in basal to suprabasal cells of well‑differentiated oral SCC, whereas cyclin D1‑positive and Ki‑67‑negative cells were present in the highly‑differentiated region, according to a double‑immunostaining method. These results indicate that the expression of cyclin D1 protein plays a role in cell differentiation and cell proliferation in well‑differentiated oral SCC.

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1	Chen YJ, Lin SC, Kao T, et al: Genome-wide profiling of oral squamous cell carcinoma. J Pathol. 204:326–332. 2004. View Article : Google Scholar : PubMed/NCBI
2	Pentenero M, Gandolfo S and Carrozzo M: Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck. 27:1080–1091. 2005. View Article : Google Scholar
3	Myers JN, Elkins T, Roberts D and Byers RM: Squamous cell carcinoma of the tongue in young adults: increasing incidence and factors that predict treatment outcomes. Otolaryngol Head Neck Surg. 122:44–51. 2000. View Article : Google Scholar
4	Motokura T, Bloom T, Kim HG, Jüppner H, Ruderman JV, Kronenberg HM and Arnold A: A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 350:512–515. 1991. View Article : Google Scholar : PubMed/NCBI
5	Bellacosa A, Almadori G, Cavallos S, et al: Cyclin D1 gene amplification in human laryngeal squamous cell carcinomas: prognostic significance and clinical implications. Clin Cancer Res. 2:175–180. 1996.
6	Michalides R, van Veelen N, Hart A, Loftus B, Wientjens E and Balm A: Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res. 55:975–978. 1995.PubMed/NCBI
7	Vora HH, Shah NG, Trivedi TT, et al: Cyclin D1 expression in prediction of survival in carcinoma of the tongue. GCRI Bulletin. 7:130–135. 1997.
8	Mishra R and Das BR: Cyclin D1 expression and its possible regulation in chewing tobacco mediated oral squamous cell carcinoma progression. Arch Oral Biol. 54:917–923. 2009. View Article : Google Scholar
9	Santarius T, Shipley J, Brewer D, Stratton MR and Cooper CS: A census of amplified and overexpressed human cancer genes. Nat Rev Cancer. 10:59–64. 2010. View Article : Google Scholar : PubMed/NCBI
10	Malumbres M and Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nature Rev Cancer. 9:153–166. 2009. View Article : Google Scholar : PubMed/NCBI
11	Bienvenu F, Jirawatnotai S, Elias JE, et al: Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature. 463:374–378. 2010. View Article : Google Scholar
12	Carlos de Vicente J, Herrero-Zapatero A, Fresno MF and López-Arranz JS: Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance. Oral Oncol. 38:301–308. 2002.PubMed/NCBI
13	Sobin LH and Wittekind C: International Union Against Cancer: TNM Classification of Malignant Tumors. 5th edition. Wiley-Liss Publications; New York, NY: 1997
14	Wang L, Liu T, Nishioka M, Aguirre RL, Win SS and Okada N: Activation of ERK1/2 and cyclin D1 expression in oral tongue squamous cell carcinomas: relationship between clinicopathological appearances and cell proliferation. Oral Oncol. 42:625–631. 2006. View Article : Google Scholar
15	Lam KY, Ng IO, Yuen AP, Kwong DL and Wei W: Cyclin D1 expression in oral squamous cell carcinomas: clinicopathological relevance and correlation with p53 expression. J Oral Pathol Med. 29:167–172. 2000. View Article : Google Scholar : PubMed/NCBI
16	Angadi PV and Krishnapillai R: Cyclin D1 expression in oral squamous cell carcinoma and verrucous carcinoma: correlation with histological differentiation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 103:e30–e35. 2007. View Article : Google Scholar
17	Bartkova J, Lukas J, Müller H, Strauss M, Gusterson B and Bartek J: Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Res. 55:949–956. 1995.PubMed/NCBI
18	Mikami T, Cheng J, Maruyama S, et al: Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ. Oral Oncol. 47:497–503. 2011. View Article : Google Scholar : PubMed/NCBI
19	Musgrove EA, Lee CS, Buckley MF and Sutherland RL: Cyclin D1 induction in breast cancer cells shortens G1 and is sufficient for cells arrested in G1 to complete the cell cycle. Proc Natl Acad Sci USA. 91:8022–8026. 1994. View Article : Google Scholar
20	Skapek SX, Rhee J, Spicer DB and Lasser AB: Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase. Science. 267:1022–1024. 1995. View Article : Google Scholar : PubMed/NCBI
21	Kotelnikov VM, Coon JS IV, Mundle S, et al: Cyclin D1 expression in squamous cell carcinomas of the head and neck and in oral mucosa in relation to proliferation and apoptosis. Clin Cancer Res. 3:95–101. 1997.PubMed/NCBI
22	Lucibello FC, Sewing A, Brüsselbach S, Bürger C and Müller R: Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts. J Cell Sci. 105:123–133. 1993.PubMed/NCBI
23	Sauter ER, Nesbit M, Litwin S, Klein-Szanto AJ, Cheffetz S and Herlyn M: Antisense cyclin D1 induces apoptosis and tumor shrinkage in human squamous carcinomas. Cancer Res. 59:4876–4881. 1999.PubMed/NCBI
24	Li Z, Jiao X, Wang C, et al: Alternative cyclin D1 splice forms differentially regulate the DNA damage response. Cancer Res. 70:8802–8811. 2010. View Article : Google Scholar : PubMed/NCBI
25	Wang J, Wang Q, Cui Y, et al: Knockdown of cyclin D1 inhibits proliferation, induces apoptosis, and attenuates the invasive capacity of human glioblastoma cells. J Neurooncol. 106:473–484. 2012. View Article : Google Scholar : PubMed/NCBI
26	Biliran H Jr, Wang Y, Banerjee S, et al: Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin Cancer Res. 11:6075–6086. 2005. View Article : Google Scholar