Establishment and characterization of a penile cancer cell line, penl1, with a deleterious TP53 mutation as a paradigm of HPV-negative penile carcinogenesis
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Jieping Chen1,2,*, Kai Yao1,2,*, Zaishang Li1,2, Chuangzhong Deng1,2, Liangjiao Wang3, Xingsu Yu1,4, Peili Liang5, Qiankun Xie1,4, Peng Chen6, Zike Qin1,2, Yunlin Ye1,2, Zhuowei Liu1,2, Fangjian Zhou1,2, Zhenfeng Zhang1,4, Hui Han1,2
1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
2Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China
3Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
4Center of Medical Imaging & Image-Guided Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
5Department of Gynecology, Sun Yat-sen Memorial Hospital, Guangzhou, China
6Department of Urology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi, China
*These authors have contributed equally to this work
Zhenfeng Zhang, email: [email protected]
Hui Han, email: [email protected]
Keywords: penile squamous cell carcinoma, lymph node metastasis, characterization, TP53, human papilloma virus-induced penile carcinogenesis
Received: November 18, 2015 Accepted: May 02, 2016 Published: June 16, 2016
Purpose: To establish penile cancer (PeCa) cell lines for the study of molecular mechanisms of carcinogenesis and testing therapeutic reagents.
Materials and Methods: We successfully established two PeCa cell lines from fresh tumor tissues from 21 cases. One cell line named Penl1 was isolated from a lymph node metastasis (LNM) of penile squamous cell carcinoma (PeSCC), usual type and comprehensively characterized here. Our in-depth characterization analysis of the Penl1 cell line included morphology, tumorigenicity, genetic characteristics, protein expression, biology, and chemosensitivity. Penl1 was authenticated by single tandem repeat (STR) DNA typing.
Results: Comparative histomorphology, genetic characteristics, and protein expression patterns revealed essential similarities between the cell line and its corresponding LNM. In-depth characterization analysis of Penl1 cell line revealed tumorigenicity in immunodeficient mice, negative human papilloma virus (HPV) and mycoplasma infection, TP53 mutations and sensitivity to cisplatin and epirubicin. STR DNA typing did not match any cell lines within three international cell banks. The limitation of this study is that one patient cannot represent the complete heterogeneity of PeCa, especially primary tumor.
Conclusions: We established and characterized an HPV-negative and moderately differentiated PeCa cell model with a TP53 missense mutation from a PeSCC, usual type patient. A preliminarily study of carcinogenesis and chemosensitivity suggests that this cell model carries a tumor suppressor gene mutation and is sensitive to chemotherapy drugs.
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