In vivo cell kinetics in breast carcinogenesis

Bai, Maria; Agnantis, Niki J.; Kamina, Sevasti; Demou, A; Zagorianakou, P; Katsaraki, Aphroditi; Kanavaros, Panayiotis

doi:10.1186/bcr306

Cited by 30 publications

(11 citation statements)

References 39 publications

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“…The apoptotic indices reported by these authors vary by an order of magnitude (0.1 to 1.2), compared with 0.3 reported in another study where morphology alone was used to identify apoptotic cells (Potten et al 1988). Studies using TUNEL report values ranging from 0.0 (Bai et al 2001) to 0.04 (Wong et al 2001), to 2.1 per terminal duct lobular unit (Feuerhake et al 2003). Using TUNEL, we have found values of 0.2% for premenopausal women, and 0.1% for postmenopausal women.…”

Section: Apoptosis In Normal Breast Epitheliummentioning

confidence: 83%

“…The measurement of apoptosis in the normal breast has been performed by the counting of apoptotic bodies on histological sections, by the TUNEL (TdT-mediated dUTP nick-end labeling) reaction, and more recently by IHC detection of activated caspase-3, which represents the final enzymatic event leading to DNA fragmentation (Gown & Willingham 2002). There is agreement that a wave of apoptosis occurs in late luteal phase (Anderson et al 1982, Williams et al 1991, and that proliferative and apoptotic rates increase as epithelium progresses from normality to malignancy (Allan et al 1992, Bai et al 2001. Two studies of apoptosis and proliferation in normal breast epithelium from women with breast cancer and those undergoing benign breast biopsy for conditions such as fibroadenoma concluded that the ratio of proliferative to apoptotic indices is higher in women with breast cancer (Allan et al 1992, Hassan & Walker 1998, suggesting that decreased elimination of epithelial cells may contribute to the development of malignancy.…”

Section: Apoptosis In Normal Breast Epitheliummentioning

confidence: 99%

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The local hormonal environment and related biomarkers in the normal breast

Khan¹,

Bhandare²,

Chatterton³

2005

Endocr Relat Cancer

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Recent developments in breast epithelial sampling techniques (nipple fluid aspiration, ductal lavage, and random fine needle aspiration) provide new opportunities for the acquisition of hormonal and cellular biomarker data in asymptomatic women, and thereby the possibility of developing a unified vision of how the hormonal environment of the breast may interact with the cellular expression of proteins, and with other evolving candidate markers of breast cancer risk. The purpose of this review is to integrate available information regarding cellular and breast fluid biomarkers of hormone action on the breast, to identify candidate biomarkers for studies of breast cancer risk and prevention. These include the estrogen receptors a and b, markers of proliferative and apoptotic response, and protein markers of estrogen action in breast cells and nipple fluid. Studies of breast hormone levels in nipple aspiration fluid (NAF) show that estrone sulphate is present in large quantities in the normal breast, while the differences in serum ovarian steroids that are seen in preand postmenopausal women are blunted in NAF. The variability of several estradiol precursors in NAF over time is relatively small, a useful attribute of potential biomarkers of breast cancer risk, particularly if they are reversible with intervention in Phase 2 prevention trials. These studies are already providing new insights into the hormonal etiology of breast cancer, and should lead to the identification of robust, reversible biomarkers for use in breast cancer prevention studies.

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Section: Apoptosis In Normal Breast Epitheliummentioning

confidence: 83%

Section: Apoptosis In Normal Breast Epitheliummentioning

confidence: 99%

The local hormonal environment and related biomarkers in the normal breast

Khan¹,

Bhandare²,

Chatterton³

2005

Endocr Relat Cancer

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“…For example, it has been widely observed that, in breast cancer, the rates of proliferation and cell death are positively correlated [58-61]. Apoptosis and necrosis are associated with both enhanced lymphocytic infiltrate in breast cancer [60] and enhanced immunogenic response [62-64].…”

Section: Discussionmentioning

confidence: 99%

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

et al. 2013

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BackgroundGene expression signatures indicative of tumor proliferative capacity and tumor-immune cell interactions have emerged as principal biology-driven predictors of breast cancer outcomes. How these signatures relate to one another in biological and prognostic contexts remains to be clarified.ResultsTo investigate the relationship between proliferation and immune gene signatures, we analyzed an integrated dataset of 1,954 clinically annotated breast tumor expression profiles randomized into training and test sets to allow two-way discovery and validation of gene-survival associations. Hierarchical clustering revealed a large cluster of distant metastasis-free survival-associated genes with known immunological functions that further partitioned into three distinct immune metagenes likely reflecting B cells and/or plasma cells; T cells and natural killer cells; and monocytes and/or dendritic cells. A proliferation metagene allowed stratification of cases into proliferation tertiles. The prognostic strength of these metagenes was largely restricted to tumors within the highest proliferation tertile, though intrinsic subtype-specific differences were observed in the intermediate and low proliferation tertiles. In highly proliferative tumors, high tertile immune metagene expression equated with markedly reduced risk of metastasis whereas tumors with low tertile expression of any one of the three immune metagenes were associated with poor outcome despite higher expression of the other two metagenes.ConclusionsThese findings suggest that a productive interplay among multiple immune cell types at the tumor site promotes long-term anti-metastatic immunity in a proliferation-dependent manner. The emergence of a subset of effective immune responders among highly proliferative tumors has novel prognostic ramifications.

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“…As mentioned, the scenarios delineated above are difficult to reconcile with the significant spontaneous apoptosis rates observed in several human tumor types which often exceed those of corresponding normal tissues [138,139,140,141,142,143,144,145,146,147,148,149]. In fact, spontaneous apoptosis occurring in malignant neoplasms was already noted in the seminal publication of Kerr et al (1972) that coined the term apoptosis [150].…”

Section: The Occurrence Of Spontaneous Apoptosis In Tumorsmentioning

confidence: 99%

“…For small cell lung carcinoma an AI of 2.65% (mean) was reported [147], for prostate cancer an AI of 1.9% [148], and for gastric cancer an AI of 1.97% [146]. Several studies on breast cancer have even demonstrated a correlation between the rate of apoptosis and tumor progression [138,139,142]. In one study [138], the AI in breast cancer varied from 0.02% for hyperplasia up to 3.69% for invasive carcinoma (median 1.17%).…”

Section: The Occurrence Of Spontaneous Apoptosis In Tumorsmentioning

confidence: 99%

The Enigmatic Roles of Caspases in Tumor Development

Jäger

Zwacka

2010

Cancers

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One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors.

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In vivo cell kinetics in breast carcinogenesis

Cited by 30 publications

References 39 publications

The local hormonal environment and related biomarkers in the normal breast

The local hormonal environment and related biomarkers in the normal breast

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

The Enigmatic Roles of Caspases in Tumor Development

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