Expression Pattern of a Homeotic Gene, HOXA5, in Normal Breast and in Breast Tumors

Abstract

Introduction: Homeotic (HOX) gene products are now known to be functionally associated with breast cancer biogenesis. Recent evidence has indicated that HOXA5 regulates both p53 and progesterone receptor expression levels in breast cancer cells. In addition, HOXA5 has been shown to interact and regulate the activity of another protein referred to as Twist. As homeotic genes play a pivotal role in development, we sought to decipher the expression pattern in both normal breast tissues and in breast carcinomas. Methods: RT-PCR and immunohistochemistry were performed, to assay the levels of HOXA5 expression, on a panel of normal breast tissue and its corresponding primary breast tumors. Results and Conclusions: We show that HOXA5 expression was maintained at stable levels at different reproductive stages of a woman's life, except during lactation. This evidence indicates that HOXA5 may play a role in maintaining the differentiated state within the breast epithelium. However, nearly 70% of all breast carcinomas had decreased HOXA5 protein levels as compared to normal breast tissues. In addition, we demonstrate that HOXA5 protein expression levels in breast carcinomas inversely co-relates with Epidermal Growth Factor Receptor (EGFR) expression. Furthermore, we found that the survival rate amongst the different low levels of HOXA5 expressing breast tumors was not significant, indicative of an early tumorigenesis process in the absence of innate levels of HOXA5 in normal breast cells.

Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

“…Henderson et al . reported that HOXA5 protein expression levels in breast carcinomas inversely correlated with EGFR expression [ 21 ]. Bruhl et al .…”

“…The binding of EGF to EGFR leads to receptor dimerization, autophosphorylation and the activation of several downstream signaling pathways, such as the MAPK pathway and the PI3K/Akt pathway, which play roles in cell proliferation, motility, and survival [ 19 ]; these pathways have also been shown to contribute to the abnormal growth of several types of human cancers [ 20 ]. Recent reports have demonstrated that HOX genes play a role in the regulation of several RTK family members, including EGFR [ 21 ], IGF1-receptor [ 22 ], and Eph-receptor [ 23 , 24 ], during development. Moreover, EGFR activation has been reported to stimulate HOXA7 expression [ 25 ].…”

HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines

“…HOX genes are a group of essential regulatory genes that normally control embryonic development and that should be in the silenced state in the adult central nervous system [ 11 - 13 ]. Recent studies have shown evidence of the aberrant expression of HOX genes in diverse cancers, including gliomas [ 14 - 18 ]. Although solid evidence exists concerning the role of HOX genes in oncogenesis and therapeutic resistance in gliomas, the exact mechanism remains unclear, and only a small number of recent studies have been published [ 9 , 10 , 18 ].…”

HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer

“…Nearly 70% of breast cancer decreased HOXA5 protein levels when compared to normal breast tissues. However, the survival rate amongst the different low levels of HOXA5 expressing breast tumors was not significant 36 . Not only in breast cancer, Kim et al found that there was no influence of HOXA5 methylation on survival in all NSCLC or at stages II-IV.…”