Abstract:DCIS = ductal carcinoma in situ; ER = estrogen receptor; HB = homeobox; HD = homeodomain; PR = progesterone receptor; RT-PCR = reverse transcription polymerase chain reaction. (Print ISSN 1465-5411; Online ISSN 1465-542X). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Breast Cancer Research Vol 5 No 4 Fu et al.
Research article
Correlation of expression of … Show more
“…Current and published work suggests a role for BP1 in carcinogenesis and progression. Based on previous work 4,5 and the present results in prostate cancer, it appears that BP1 is involved in the carcinogenic sequence as it appears to be expressed in 46% of ductal carcinomas in situ of the breast and all the examples of PIN identified in prostate cancer sections. Moreover, BP1 appears to be involved in cellular proliferation and in altering or blocking the pathway of programmed cell death (apoptosis).…”
Section: Discussionsupporting
confidence: 68%
“…This study demonstrates that the frequency and intensity of BP1 expression, as measured by immunohistochemical reactivity, increases within PIN and prostatic carcinoma relative to benign acinar glands and that the extent and intensity of the 4,5 Analogous to breast cancers, BP1 immunoreactivity was not present in normal prostatic tissue, but demonstrated diffuse and strong immunoreactivity within neoplastic cells of PIN and invasive adenocarcinoma.…”
Section: Discussionmentioning
confidence: 65%
“…3 Our studies in breast cancer have demonstrated that BP1 expression was present in 80% of infiltrating duct carcinomas and relatively absent in matched normal controls. 4,5 We have also shown that BP1 expression was significantly higher in cancers that were estrogen receptor negative relative to estrogen receptor positive breast tumors and in African Americans than in Caucasians. 4 BP1 demonstrates significant expression in breast cancers with a relative aggressive phenotype, namely, estrogen receptor negative and inflammatory breast cancers, and consequently, we may propose several analogies that may be relevant to prostate cancers.…”
mentioning
confidence: 83%
“…4,5 We have also shown that BP1 expression was significantly higher in cancers that were estrogen receptor negative relative to estrogen receptor positive breast tumors and in African Americans than in Caucasians. 4 BP1 demonstrates significant expression in breast cancers with a relative aggressive phenotype, namely, estrogen receptor negative and inflammatory breast cancers, and consequently, we may propose several analogies that may be relevant to prostate cancers. Invasive cancers are believed to result from a progressive, multi-step process initiated and driven by a sequential accumulation of genetic and biochemical abnormalities.…”
BP1 is a member of the homeobox gene superfamily of transcription factors that are essential for early development. Significant mRNA expression and immunohistochemical reactivity of BP1 is present in a majority of breast cancers and in all cases of inflammatory breast cancer. This study attempts to determine whether BP1 expression is detectable in prostate cancer, another hormone dependent solid tumor, and whether this expression correlates with histopathologic and prognostic factors. Paraffin sections from radical prostatectomy cancer specimens and from tissue microarray sections of prostate cancer, obtained from the Prostate Cancer Tissue Registry (NIH), were assayed for BP1 immunoreactivity. Immunoreactivity scoring by two independent pathologists, using a three-tiered system (0, 1 þ , 2 þ ), was recorded and correlated with Gleason scoring and prostatic specific antigen (PSA) biochemical recurrence. Ki-67 (MIB-1) immunoreactivity was performed to assess proliferation. Kappa and Cochran-Mantel-Haenszel statistical analyses were used to assess interobserver agreement and pathobiologic correlations. Significant BP1 immunoreactivity (2 þ ) was identified in approximately 70% of prostatic adenocarcinomas, whether the analysis was performed on tissue sections (50 cases) or tissue microarray platforms (123 cases). BP1 immunoreactivity was seen in o5% of normal acinar cells. The agreement between two separate observers was very good, with kappa-statistics 40.7. In tissue sections, 12 cases with paired carcinoma and prostatic intraepithelial neoplasia (PIN) showed concordance with strong immunoreactivity. Gleason scores or prostatic specific antigen (PSA) biochemical recurrences were not correlated with strong BP1 immunoreactivity. Tumor proliferation, assayed with Ki-67 (MIB-1) immunoreactivity, was higher in cancer cells that were BP1 immunoreactive, relative to those that were BP1 non-reactive. These findings suggest that BP1 is an important upstream factor in the carcinogenic pathway of prostate cancer and that the expression of BP1 may reflect or directly contribute to tumor progression and/or invasion.
“…Current and published work suggests a role for BP1 in carcinogenesis and progression. Based on previous work 4,5 and the present results in prostate cancer, it appears that BP1 is involved in the carcinogenic sequence as it appears to be expressed in 46% of ductal carcinomas in situ of the breast and all the examples of PIN identified in prostate cancer sections. Moreover, BP1 appears to be involved in cellular proliferation and in altering or blocking the pathway of programmed cell death (apoptosis).…”
Section: Discussionsupporting
confidence: 68%
“…This study demonstrates that the frequency and intensity of BP1 expression, as measured by immunohistochemical reactivity, increases within PIN and prostatic carcinoma relative to benign acinar glands and that the extent and intensity of the 4,5 Analogous to breast cancers, BP1 immunoreactivity was not present in normal prostatic tissue, but demonstrated diffuse and strong immunoreactivity within neoplastic cells of PIN and invasive adenocarcinoma.…”
Section: Discussionmentioning
confidence: 65%
“…3 Our studies in breast cancer have demonstrated that BP1 expression was present in 80% of infiltrating duct carcinomas and relatively absent in matched normal controls. 4,5 We have also shown that BP1 expression was significantly higher in cancers that were estrogen receptor negative relative to estrogen receptor positive breast tumors and in African Americans than in Caucasians. 4 BP1 demonstrates significant expression in breast cancers with a relative aggressive phenotype, namely, estrogen receptor negative and inflammatory breast cancers, and consequently, we may propose several analogies that may be relevant to prostate cancers.…”
mentioning
confidence: 83%
“…4,5 We have also shown that BP1 expression was significantly higher in cancers that were estrogen receptor negative relative to estrogen receptor positive breast tumors and in African Americans than in Caucasians. 4 BP1 demonstrates significant expression in breast cancers with a relative aggressive phenotype, namely, estrogen receptor negative and inflammatory breast cancers, and consequently, we may propose several analogies that may be relevant to prostate cancers. Invasive cancers are believed to result from a progressive, multi-step process initiated and driven by a sequential accumulation of genetic and biochemical abnormalities.…”
BP1 is a member of the homeobox gene superfamily of transcription factors that are essential for early development. Significant mRNA expression and immunohistochemical reactivity of BP1 is present in a majority of breast cancers and in all cases of inflammatory breast cancer. This study attempts to determine whether BP1 expression is detectable in prostate cancer, another hormone dependent solid tumor, and whether this expression correlates with histopathologic and prognostic factors. Paraffin sections from radical prostatectomy cancer specimens and from tissue microarray sections of prostate cancer, obtained from the Prostate Cancer Tissue Registry (NIH), were assayed for BP1 immunoreactivity. Immunoreactivity scoring by two independent pathologists, using a three-tiered system (0, 1 þ , 2 þ ), was recorded and correlated with Gleason scoring and prostatic specific antigen (PSA) biochemical recurrence. Ki-67 (MIB-1) immunoreactivity was performed to assess proliferation. Kappa and Cochran-Mantel-Haenszel statistical analyses were used to assess interobserver agreement and pathobiologic correlations. Significant BP1 immunoreactivity (2 þ ) was identified in approximately 70% of prostatic adenocarcinomas, whether the analysis was performed on tissue sections (50 cases) or tissue microarray platforms (123 cases). BP1 immunoreactivity was seen in o5% of normal acinar cells. The agreement between two separate observers was very good, with kappa-statistics 40.7. In tissue sections, 12 cases with paired carcinoma and prostatic intraepithelial neoplasia (PIN) showed concordance with strong immunoreactivity. Gleason scores or prostatic specific antigen (PSA) biochemical recurrences were not correlated with strong BP1 immunoreactivity. Tumor proliferation, assayed with Ki-67 (MIB-1) immunoreactivity, was higher in cancer cells that were BP1 immunoreactive, relative to those that were BP1 non-reactive. These findings suggest that BP1 is an important upstream factor in the carcinogenic pathway of prostate cancer and that the expression of BP1 may reflect or directly contribute to tumor progression and/or invasion.
“…In earlier study in which semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate BP1 expression, BP1 was active in 80% of invasive ductal breast tumors, where 100% of ER-negative tumors were BP1 positive, compared with 73% of ER-positive tumors (p = 0.03) [33]. BP1 expression may also be associated with race: 89% of the tumors of African-American women expressed BP1 while 57% of Caucasian women showed BP1 positivity (p = 0.04).…”
Homeobox genes are critical in tumor development. An isoform protein of DLX4 called BP1 is expressed in 80% of invasive ductal breast carcinomas. BP1 overexpression is implicated in an aggressive phenotype and poor prognosis. BP1 upregulation is associated with estrogen receptor negativity so those tumors do not respond to antiestrogens. Breast cancer is the second leading cause of death in women. BP1 could serve as both a novel prognostic biomarker for breast cancer and a therapeutic target. In this review, we address the role of BP1 protein in tumorigenesis of breast cancer and four other malignancies. A number of functions of BP1 in cancer are also discussed. Female breast cancer represents 14.6% of all new cancer cases in the USA according to the National Cancer Institute [1]. An estimated 252,710 new cases of invasive breast cancer are expected to be diagnosed in women in the USA in 2017. It is also estimated that 30% of newly diagnosed cancers in women will be breast cancers [2].Breast cancer is a hormone-dependent cancer, and estrogen (17β-estradiol) plays a critical role in the initiation and the progression of this disease [3]. Estrogen, produced by the ovaries, affects the growth and function of mammary glands by binding to the estrogen receptors (ERs) α and β. Through dimerization of the receptor, translocation to the nucleus and interaction with estrogen response elements in the promoter region of targeted genes, gene expression leads to multiple biological outcomes [4]. 70% of invasive breast cancers are ER positive (ER + ), making antiestrogens essential in treating these patients [5]. Targeting the ER or its pathway using tamoxifen (a selective ER modulator) or fulvestrant (an ER downregulator) have been successful therapeutic strategies [6]. However, drug resistance remains a major challenge in treating breast cancer. The main pathway leading to resistance involves loss of ER expression or selection of an ER-negative population of cells. Moreover, these ER-negative breast cancers have a higher histologic grade and a higher proliferative rate and are associated with poorer prognosis. This highlights the key importance of finding alternative targets to treat these patients and identifying a new biomarker for breast cancer prognosis.BP1 protein, an isoform of DLX4, belongs to the homeobox gene family which includes regulatory genes implicated in early development and cell differentiation that are frequently dysregulated in cancer [7]. Therefore, targeting BP1 may provide a new avenue for breast cancer management. The first related paper was published in 1998, when the authors mapped this new homeobox gene to chromosome 17q21 and characterized its role in repression of the β-globin gene [8]. During the last 20 years, several studies have been carried out to measure BP1 levels in breast cancer and other carcinomas, with the primary aim of confirming its diagnostic and prognostic value as a biomarker. We are writing this review to consolidate and update all of the available information on BP1.
Homeobox...
TALE homeodomain proteins are an ancient subgroup within the group of homeodomain transcription factors that play important roles in animal, plant, and fungal development. We have extracted the full complement of TALE superclass homeobox genes from the genome projects of seven protostomes, seven deuterostomes, and Nematostella. This was supplemented with TALE homeobox genes from additional species and phylogenetic analyses were carried out with 276 sequences. We found 20 homeobox genes and 4 pseudogenes in humans, 21 genes in mouse, 8 genes in Drosophila, and 5 genes plus one truncated gene in Caenorhabditis elegans. Apart from the previously identified TALE classes MEIS, PBC, IRO, and TGIF, a novel class is identified, termed MOHAWK (MKX). Further, we show that the MEIS class can be divided into two families, PREP and MEIS. Prep genes have previously only been described in vertebrates but are lacking in Drosophila. Here we identify orthologues in other insect taxa as well as in the cnidarian Nematostella. In C. elegans, a divergent Prep protein has lost the homeodomain. Full-length multiple sequence alignment of the protostome and deuterostome sequences allowed us to identify several novel conserved motifs within the MKX, TGIF, and MEIS classes. Phylogenetic analyses revealed fast-evolving PBC class genes; in particular, some X-linked PBC genes in nematodes are subject to rapid evolution. In addition, several instances of gene loss were identified. In conclusion, our comprehensive analysis provides a defining framework for the classification of animal TALE homeobox genes and the understanding of their evolution.
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