αB-crystallin: A novel marker of invasive basal-like and metaplastic breast carcinomas

Sitterding, Stephanie; Wiseman, William R.; Schiller, Carol L.; Luan, Chunyan; Chen, Feng; Moyano, José V.; Watkin, William; Wiley, Elizabeth L.; Cryns, Vincent L.; Diaz, Leslie K.

doi:10.1016/j.anndiagpath.2007.02.004

Cited by 62 publications

(64 citation statements)

References 32 publications

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“…5 More recently, a subgroup of lobular carcinomas has been shown to express high-molecular-weight cytokeratins, 41 however it remains to be determined whether these cases truly show a basal-like transcriptome. The majority of basal-like breast cancers lack or show low levels of ER and PR, lack HER2 protein overexpression and HER2 gene amplification, whereas they express genes and proteins usually found in 'basal'/myoepithelial cells of the normal breast including high-molecular-weight cytokeratins (5/6, 14 and 17), 17,19,21,42 P-cadherin, 43 caveolins 1 and 2, 44,45 nestin, 46 aB crystallin, 47,48 CD109, 49,50 and EGFR 17 and, in a minority of cases, harbor EGFR gene amplification 51 or aneusomy. 52 p53 immunohistochemical expression or TP53 gene mutations is observed in up to 85% of cases, 53,54 and alterations of the pRB and p16 G1/S cell-cycle checkpoint are remarkably prevalent in these cancers.…”

Section: What Is a Basal-like Breast Cancer?mentioning

confidence: 99%

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

et al. 2011

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Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

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Section: What Is a Basal-like Breast Cancer?mentioning

confidence: 99%

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

et al. 2011

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“…24,25 While its chaperone activity and its contribution to myopathies, gliopathies and neurodegenerative diseases have been well documented, 24,25 the molecular understanding of αB-crystallin's role in cancer is only beginning to emerge. High levels of αB-crystallin expression have been reported in various cancer types, including prostate cancer, 26 oral squamous cell carcinomas, 27 renal cell carcinomas, 26,28 basal-like breast carcinomas 29 and gliomas. [30][31][32] Expectedly, αB-crystallin possesses various tumorigenesis-relevant activities, such as transforming, anti-apoptotic, and invasive properties.…”

Section: αB-crystallin Is a Novel Gliomagenic Oncoproteinmentioning

confidence: 99%

What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? A role for Bcl2L12 as a multifunctional cell death regulator

Stegh¹,

Chin²,

Louis³

et al. 2008

Cell Cycle

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Glioblastoma (GBM) is the most common type of primary brain cancer and carries a dismal prognosis primarily due to the emergence of resistance towards extant radiation, conventional and targeted chemotherapies. Although GBM resists therapy-induced apoptosis, tumors show a seemingly paradoxical propensity for florid intratumoral necrogenesis. This necrosis manifests pathologically as microscopic foci or confluent expanses of necrotic tumor. While it is now well recognized that necrosis is an active cell death process and that apoptosis and necrosis death modalities are intertwined on multiple levels, the precise molecular mechanisms and genetic elements underlying these forms of cell death in GBM remain areas of active investigation. In recent oncogenomic studies, we identified a novel GBM oncoprotein, Bcl2-Like 12 (Bcl2L12), which is significantly expressed in the majority of primary GBM tumor specimens and distantly related to canonical Bcl-2 proteins. Due to its distinctive impact on cell death signaling, Bcl2L12 phenocopies pro-necrotic and anti-apoptotic propensities of highgrade glioma: Mechanistically, we determined that unlike prototypic Bcl-2 family members, Bcl2L12 does not safeguard mitochondrial membrane integrity, but instead potently inhibits apoptosis at the level of post-mitochondrial effector caspase-3/7 activation. A combination of enforced expression, RNAi-mediated extinction, co-localization and protein interaction studies revealed that Bcl2L12 inhibits caspases 3 and 7 via distinct mechanisms. Direct physical interaction underlies Bcl2L12's inhibition of caspase-7 processing, whereas Bcl2L12-induced transcriptional upregulation of the small heat shock protein αB-crystallin is instrumental to neutralization of caspase-3 activation. Mirroring the cellular phenotype elicited by energy depletion, genetic or pharmacologic inhibition of post-mitochondrial apoptosis signaling molecules, Bcl2L12 promotes necrogenesis in glial cells in the context of a proapoptotic stimulus establishing that it represents a novel regulator of the balance between apoptosis and necrosis in GBM.

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“…It is crucial to note, however, that although most basal-like cancers are triple-negative breast cancer, there is moderate discordance between triple-negative breast cancer and basal-like breast cancer (5,6). In addition to variability in expression of known basal markers, there is also heterogeneity within triple-negative breast cancer for other potentially relevant features including p53 mutation, BRCA1 mutation or expression (7), expression of aBcrystallin (8,9), and degree of expression of immune response genes (refs. 5, 10; Fig.…”

mentioning

confidence: 99%

Triple-Negative Breast Cancer: Risk Factors to Potential Targets

Schneider

Winer

Foulkes

et al. 2008

Clinical Cancer Research

391

347

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Triple-negative breast cancer has recently been recognized as an important subgroup of breast cancer with a distinct outcome and therapeutic approach when compared with other subgroups of breast cancer. Triple-negative breast cancer comprises primarily, but not exclusively, a molecularly distinct subtype of breast cancer, the basal-like subtype. We do not yet have an assay to identify basal-like breast cancer in clinical samples, so triple-negative breast cancer has become a commonly used proxy for this subtype. The molecular biology and pathophysiology of triplenegative breast cancer are not completely understood, but understanding is improving rapidly with the advent of sophisticated molecular biology platforms. Moreover, the established risk factors of breast cancer as a whole may not apply to this unique subgroup of patients. Finally, because triple-negative breast cancer is defined by the absence of a target, there are currently limitations to using a tailored therapeutic approach, leaving conventional cytotoxic therapies as the mainstay. Active preclinical and clinical research programs focus on defining the clinical behavior, delineating the risk factors, and more completely understanding the molecular biology of triple-negative breast cancer to improve prevention, optimize conventional agents, and unveil novel therapeutic targets. This CCR focus article will review the current state of the art on triplenegative breast cancer.Triple-negative breast cancer [estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 (HER2) negative] remains a major challenge to physicians and patients, and a source of great interest to laboratory investigators. Although triple-negative breast cancer accounts for a relatively small minority of breast cancer cases, it is responsible for a disproportionate number of breast cancer deaths. Moreover, there have been fewer advances in the treatment of triple-negative breast cancer than have been seen with other subtypes. For these reasons, new research initiatives for triple-negative breast cancer are critical. The investigation of triple-negative breast cancer is one facet of an emerging effort that regards breast cancer as a collection of separate diseases rather than a single heterogeneous entity, an important step toward the individualization of therapy (1). Here we attempt to (a) define triple-negative breast cancer and compare and contrast it with basal-like disease (a term frequently used interchangeably with triple-negative disease); (b) outline established and proposed risk factors; (c) review the molecular, pathologic, and clinical features of triple-negative disease; (d) provide an overview of ongoing therapeutic trials; and (e) suggest possible avenues for future research.Triple-Negative or Basal-like Breast Cancer: Which Is It?Triple-negative breast cancer has become a commonly used descriptor for malignancies that are estrogen receptor, progesterone receptor, and HER2 negative. The recent focus on this subgroup of...

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αB-crystallin: A novel marker of invasive basal-like and metaplastic breast carcinomas

Cited by 62 publications

References 32 publications

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? A role for Bcl2L12 as a multifunctional cell death regulator

Triple-Negative Breast Cancer: Risk Factors to Potential Targets

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