Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27

O'Neill, Penny; Shaaban, Abeer M.; West, Christopher R.; Dodson, Andrew; Jarvis, Christine; Moore, Pascale; Davies, Michael; Sibson, D. Ross; Foster, Christopher S.

doi:10.1038/sj.bjc.6601449

Cited by 41 publications

(33 citation statements)

References 24 publications

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“…11 Furthermore, during the initiation and promotion of human breast cancers, the expression of hsp27 increases. 28 The finding that a number of heat shock proteins are overexpressed in the early stages of carcinogenesis with DMBA (shown here) as well as with PhIP 5 further implicates heat shock proteins in breast cancer development.…”

Section: Discussionmentioning

confidence: 96%

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Papaconstantinou

Shanmugam

Shan

et al. 2005

Intl Journal of Cancer

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Identification of molecular markers of early‐stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12‐dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real‐time PCR, RT‐PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of β‐casein and transferrin and higher expression of hsp27 in glands from DMBA‐treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki‐67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, α‐tubulin and hsp27, were all overexpressed in the mammary gland of DMBA‐treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 96%

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Papaconstantinou

Shanmugam

Shan

et al. 2005

Intl Journal of Cancer

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“…Unfortunately, most previous RT -PCR analysis studies have used primers unsuitable for distinguishing individual isoforms. Recent production of antibodies suitable for detection of individual ERb isoforms (Saunders et al, 2002;Skliris et al, 2002) should allow a better understanding of the complex factors regulating hormone responsiveness of human breast carcinomas to emerge (O'Neill et al, 2003;Shaaban et al, 2003b). …”

Section: Discussionmentioning

confidence: 99%

Wild-type oestrogen receptor beta (ERβ1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers

et al. 2004

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This study has tested the hypothesis that comparison of protein and mRNA expression for ERa and ERb1 by human breast cancers provides novel information relating to the clinical and pathological characteristics of human breast cancers. Expression of ERa and ERb1 was identified in 167 invasive cancers from postmenopausal women treated only with endocrine therapy. The cohort included 143 cases receiving only adjuvant Tamoxifen following surgery. ERa and ERb1 expression was analysed by immunohistochemistry and reverse transcription RT -PCR and compared with clinical progression of individual cancers. ERa protein was closely associated with the corresponding RNA detected by RT -PCR (Chi-square, Po0.001). In contrast, ERb1 protein and mRNA were inconsistent. Although an association was identified between ERa and ERb mRNAs (Chi-square, Po0.001) and between ERa protein and ERb1 mRNA (Chi-square, Po0.027), no association was identified for the ERa and ERb1 proteins detected by immunohistochemistry. ERb1 was not associated with outcome. However, in the absence of ERa, ERb1 protein expression was associated with elevated cell proliferation. There was a trend for the ERb1 protein-positive cases to have a worse outcome, both within the group as a whole as well as within the ERa-positive Tamoxifen-treated cases. This study has confirmed the hypothesis that expression of ERa is an important determinant of breast cancer progression, and has further demonstrated that ERb1 may play a role in the response of breast cancers to endocrine therapy.

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“…Interestingly, previous studies have showed that HSPB1 was overexpressed in preneoplastic lesions in the uterine cervix and gastric cancer, and has an early diagnostic significance for these two tumors (56,57), which also supports HSPB1 as biomarker for early detection of LSCC. It has been reported that HSPB1 overexpression was involved in liver carcinogenesis induced by chemical carcinogens (58), and HSPB1 expression in benign proliferating breast lesions increased risk of cell malignant progression (59). Therefore, it is conceivable that HSPB1 up-regulation may confer a higher susceptibility of human bronchial epithelial cells to carcinogenic stimuli, and contribute to cell survival and growth advantage, leading to evolution of bronchial epithelial carcinogenesis.…”

Section: Knockdown Of Gstp1 Increased the Susceptibility Of Human Bromentioning

confidence: 99%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffinembedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplatic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo ( Lung cancer is the most frequently occurring malignancy with increasing incidence and is the leading cause of mortality in cancer-related deaths in China and worldwide (1, 2). Although great improvement has been made in diagnosis and treatment of lung cancer, the overall patients' survival is still very low and does not exceed 15% (3). The poor prognosis of this cancer is mainly explained by the fact that the diagnosis is generally made only at advanced stages because of the lack of reliable, early diagnostic biomarkers and the limited understanding of its carcinogenic mechanisms. Therefore, identification of biomarkers for early detection of lung cancer is mandatory, in turn leading to more effective treatment and reduction of mortality.Lung squamous cell carcinoma (LSCC) 1 originated from the bronchial epithelial cells is the most common histological type of lung cancer. It is known that carcinogenesis of LSCC is a multistage process and the result of multistep accumulation of genetic and epigenetic alterations (4). With exposure to environmental carcinogens, bronchial epithelial carcinogenesis often progresses in the following manner: hyperplasia, squamous metaplasia (SM), atypical hyperplasia (AH), cancer in situ (CIS) and invasive cancer (5). LSCC is the end-point of a whole range of morphological abnormalities that are dis-...

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Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27

Cited by 41 publications

References 24 publications

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Wild-type oestrogen receptor beta (ERβ1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

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