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Tumor Biology

, Volume 37, Issue 5, pp 6135–6142 | Cite as

HER2/ERBB2 immunoreactivity in human retinoblastoma

  • G. M. Seigel
  • S. Sharma
  • A. S. Hackam
  • Dhaval K. Shah
Original Article

Abstract

Retinoblastoma (RB) is an ocular malignancy of early childhood. Although mutations in the Rb1 gene and expression of stem cell markers have been identified in RB, additional information on RB-specific alterations in signaling pathways and protein expression would be useful for the design of targeted RB therapies. Here we have evaluated the expression of HER2 (ERBB2) in RB. HER2 is a member of the epidermal growth factor family, which is overexpressed in breast, ovarian, gastric, colorectal, pancreatic, and endometrial cancers in a stratified manner. Overexpression and gene amplification of HER2 is associated with aggressive malignancies, accompanied by chemoresistance and poor outcomes. In this study, we present the first evidence of HER2 immunoreactivity in retinoblastoma, as shown by immunocytochemistry, flow cytometry, and western immunoblot, with validation by reverse transcription PCR (RT-PCR) in both RB cell lines and clinical RB tumors. Our results suggest that the HER2 protein expressed in RB is a truncated version that spares the trastuzumab binding site, while HER2 is not detected in normal ocular tissues. Our discovery of HER2 expression in RB may lead to innovative and targeted drug treatment options designed to spare the eye and preserve vision in RB patients.

Keywords

Retinoblastoma HER2 ERBB2 Target discovery Drug target Targeted therapy 

Notes

Acknowledgments

The authors thank Dr. Bruce Ksander for providing the RB116 and RB143 cells. We also thank Dr. John Ludlow for providing the WERI-RB27 cells. GMS is supported by the Cornell Center on the Microenvironment and Metastasis through Award Number U54CA143876 from the National Cancer Institute, as well as a grant from the SUNY Brain Network of Excellence. ASH is supported by the Karl Kirchgessner Foundation. Institutional support to Bascom Palmer Eye Institute was provided by a Research to Prevent Blindness Unrestricted Grant and an NEI Center Core Grant P30 EY014801. SS is supported by a Postdoctoral Fellowship grant from Roche Inc. to DKS. This work was in part supported by NIH grant GM114179 to DKS, and funding from the Center for Protein Therapeutics at the State University of New York at Buffalo.

Authors’ contributions

All authors (GMS, SS, ASH, and DKS) participated in experimental design, analysis, and manuscript preparation. GMS carried out immunohistochemical and immunocytochemical experiments and analysis. SS performed western blot and flow cytometry with analysis. ASH provided RT-PCR results and analysis. All authors have read and approved of the final manuscript.

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Center for Hearing & Deafness, SUNY Eye InstituteUniversity at BuffaloBuffaloUSA
  2. 2.Department of Pharmaceutical SciencesUniversity at BuffaloBuffaloUSA
  3. 3.Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of MedicineUniversity of MiamiMiamiUSA

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