HAX-1 overexpression, splicing and cellular localization in tumors

Alicja Trebinska,Karolina Ciosek,Ewa A Grzybowska,Alina Rembiszewska,Konrad Ptaszynski,Janusz A Siedlecki,Sebastian Rowinski,Jolanta Kupryjanczyk

doi:10.1186/1471-2407-10-76

Abstract

BackgroundHAX-1 has been described as a protein potentially involved in carcinogenesis and especially metastasis. Its involvement in regulation of apoptosis and cell migration along with some data indicating its overexpression in cancer cell lines and tumors suggests that HAX-1 may play a role in neoplastic transformation. Here we present the first systematic analysis of HAX-1 expression in several solid tumors.MethodsUsing quantitative RT-PCR, we have determined the mRNA levels of HAX1 splice variant I in several solid tumors. We have also analyzed by semiquantitative and quantitative RT-PCR the expression of five HAX-1 splice variants in breast cancer samples and in normal tissue from the same individuals. Quantitative PCR was also employed to analyze the effect of estrogen on HAX1 expression in breast cancer cell line. Immunohistochemical analysis of HAX-1 was performed on normal and breast cancer samples.ResultsThe results reveal statistically important HAX1 up-regulation in breast cancer, lung cancer and melanoma, along with some minor variations in the splicing pattern. HAX-1 up-regulation in breast cancer samples was confirmed by immunohistochemical analysis, which also revealed an intriguing HAX-1 localization in the nuclei of the tumor cells, associated with strong ER status.ConclusionHAX-1 elevated levels in cancer tissues point to its involvement in neoplastic transformation, especially in breast cancer. The connection between HAX-1 nuclear location and ER status in breast cancer samples remains to be clarified.

Highlights

HAX-1 has been described as a protein potentially involved in carcinogenesis and especially metastasis
HAX-1 was demonstrated to interact with proteins involved in mitochondrial membrane permeabilization and elements of the mitochondrial mega-channel [4,5] as well as with proteins directly involved in initiation and execution of apoptosis [2,6,7] and with several viral proteins important for cell survival [1,8,9]
HAX1 expression level is elevated in breast and lung cancers and in melanoma In a preliminary screen, performed in order to asses HAX1 expression levels in different solid tumors, a survey panel containing cDNA from 96 tissue samples, covering 8 different cancers was used (TissueScan Oncology Survey Tissue quantitative polymerase chain reaction (qPCR) Array I)

Summary

Introduction

HAX-1 has been described as a protein potentially involved in carcinogenesis and especially metastasis. Its involvement in regulation of apoptosis and cell migration along with some data indicating its overexpression in cancer cell lines and tumors suggests that HAX-1 may play a role in neoplastic transformation. HAX-1 (HS1 associated protein X-1, encoded by the HAX1 gene) is an important target of study in the field of cancer research on account of its involvement in regulation of apoptosis and cell migration, key processes in carcinogenesis and metastasis. The most explicit role of HAX-1 has been suggested by the studies on the pathogenesis of severe congenital neutropenia (Kostmann disease). This immuno-deficiency syndrome is characterized by the paucity of neutrophils in peripheral blood caused by a block in promyelocyte/myelocyte maturation, associated with their apoptosis. HAX1 mutations, leading to the inactivation of the protein, were found in Kostmann patients, indicating the involvement of HAX-1 in the functioning of the immunological system as well as in apoptosis [10]

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