Prognostic significance of Claudin 12 in estrogen receptor-negative breast cancer

Iravani, Omid; Yip, George; Thike, Aye Aye; Chua, Pei Jou; Scully, Olivia Jane; Tan, Puay‐Hoon; Bay, Boon‐Huat

doi:10.1136/jclinpath-2015-203265

Cited by 8 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The evaluation of claudins expression was also suggested to increase the possibility of creating new drugs. Iravani and co-workers showed that expression of claudin-12 is upregulated in estrogen receptor (ER)-negative breast cancer and its expression is associated with poor prognosis, indicating that claudin-12 may serve as a marker for predicting the survival in this cancer subtype [79]. The overexpression of claudin-6 was showed to inhibit migration and invasion of MCF-7 cells [104].…”

Section: Claudins In Breast Cancermentioning

confidence: 99%

Claudins: New Players in Human Fertility and Reproductive System Cancers

Kozieł

Kowalska

Piastowska-Ciesielska

2020

Cancers

View full text Add to dashboard Cite

Claudins are major integral proteins of tight junctions (TJs), the apical cell-cell adhesions that enable maintaining polarity of epithelial cells, their differentiation, and cell signaling. A number of studies have indicated that claudins might play a crucial role in both physiology and pathogenesis. Their tissue-specific expression was originally linked to the development of different types of cancer and triggered a hope to use them as diagnostic or prognostic markers. However, it seems that their expression is more complex than that, and undoubtedly, claudins participate in one of the most important molecular events in cells. This review summarizes the recent research evaluating the role of claudins in fertility and the most common endocrine-dependent cancers in the reproductive system and highlights the crucial role of claudins both in human fertility and the most common cancers.

show abstract

Section: Claudins In Breast Cancermentioning

confidence: 99%

Claudins: New Players in Human Fertility and Reproductive System Cancers

Kozieł

Kowalska

Piastowska-Ciesielska

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…The non-canonical claudins-12 and -25 were also expressed at levels above background in both pregnancy and lactation with significant increases during lactation. There is a little data on mammary claudin-12; it showed weak cytoplasmic staining in normal breast cells adjacent to breast tumors, but was upregulated in some tumors [59]. Its expression increased MCF-7 cell migration [60], but nothing is currently known about its function in the normal mammary epithelium.…”

Section: Part 2: Claudin Expression and Localization During Mammary Gmentioning

confidence: 99%

Developmental Expression of Claudins in the Mammary Gland

Baumgartner

Rudolph

Ramanathan

et al. 2017

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

Claudins are a large family of membrane proteins whose classic function is to regulate the permeability of tight junctions in epithelia. They are tetraspanins, with four alpha-helices crossing the membrane, two extracellular loops, a short cytoplasmic N-terminus and a longer and more variable C-terminus. The extracellular ends of the helices are known to undergo side-to-side (cis) interactions that allow the formation of claudin polymers in the plane of the membrane. The extracellular loops also engage in head-to-head (trans) interactions thought to mediate the formation of tight junctions. However, claudins are also present in intracellular structures, thought to be vesicles, with less well-characterized functions. Here, we briefly review our current understanding of claudin structure and function followed by an examination of changes in claudin mRNA and protein expression and localization through mammary gland development. Claudins-1, 3, 4, 7, and 8 are the five most prominent members of the claudin family in the mouse mammary gland, with varied abundance and intracellular localization during the different stages of post-pubertal development. Claudin-1 is clearly localized to tight junctions in mammary ducts in non-pregnant non-lactating animals. Cytoplasmic puncta that stain for claudin-7 are present throughout development. During pregnancy claudin-3 is localized both to the tight junction and basolaterally while claudin-4 is found only in sparse puncta. In the lactating mouse both claudin-3 and claudin-8 are localized at the tight junction where they may be important in forming the paracellular barrier. At involution and under challenge by lipopolysaccharide claudins −1, −3, and −4 are significantly upregulated. Claudin-3 is still colocalized with tight junction molecules but is also distributed through the cytoplasm as is claudin-4. These largely descriptive data provide the essential framework for future mechanistic studies of the function and regulation of mammary epithelial cell claudins.Electronic supplementary materialThe online version of this article (doi:10.1007/s10911-017-9379-6) contains supplementary material, which is available to authorized users.

show abstract

“…Claudins are known to act as barriers for the diffusion of solutes between epithelial cells, participating in the regulation of water transportation, ions and certain macromolecules. Therefore, it is a reasonable hypothesis that claudins are likely to be involved in carcinogenesis (18). …”

Section: Introductionmentioning

confidence: 99%

“…However, the claudin superfamily of integral membrane proteins is composed of numerous isotypes (15,16,18), and there is some heterogeneity in study results when claudin subtypes are evaluated. Claudin 1 has been identified as a novel survival factor in basal-like breast cancers, as downregulation of claudin 1 was shown to induce cell death in breast cancer cell lines (17).…”

Section: Introductionmentioning

confidence: 99%

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

et al. 2018

View full text Add to dashboard Cite

Molecular phenotyping and tissue microarray (TMA) studies have identified distinct invasive breast carcinoma subtypes: Luminal A, luminal B, enriched with overexpressed human epidermal growth factor receptor 2 (HER-2) and triple-negative, i.e., negative for HER-2, as well as for estrogen and progesterone receptor (ER and PR, respectively) expression. These subtypes are useful in clinical management, since they bear distinct prognoses and predictive responses to targeted therapy. However, although molecular profiling provides important prognostic indicators, breast cancer risk stratification remains a challenge in triple-negative cases. What is referred to as claudin-low subtype was identified as a triple-negative subset that is associated with more aggressive tumor behavior and worse prognosis. However, the immunohistochemical expression of claudins has not yet been standardized. Our objective was to verify whether the immunoexpression of claudins 4 and 7 (the main claudins specifically expressed in human breast tissue) in TMA is associated with survival and prognosis in luminal A, HER-2 and triple-negative molecular subtypes. In this diagnostic study, we investigated ER/PR receptor status, HER-2, claudin 4 and 7 expression and stem cell CD44/24 profiles, and verified the association with prognosis and survival outcomes in 803 invasive breast carcinoma cases arranged in four TMAs. Among these, 503 (62.6%) were positive for claudin 4 and 369 (46.0%) for claudin 7. Claudin 4 exhibited the lowest expression in luminal A and triple-negative subtypes, and the highest frequency of expression in HER-2-enriched subtypes, whereas claudin 7 staining was not associated with any subtype. The stem cell phenotype was not associated with subgroups or claudins 4 and 7. Claudin immunoexpression profile was not able to distinguish between patients with better or worse prognosis, and it was not correlated to triple-negative cases. Therefore, it may be concluded that the immunoexpression of claudins 4 and 7, individually or within the usual immunohistochemical context (ER, PR and HER-2), does not provide additional prognostic information on breast cancer subtypes.

show abstract

Prognostic significance of Claudin 12 in estrogen receptor-negative breast cancer

Abstract: The findings suggest that CLDN 12 expression could be clinically useful for predicting the survival of the ER-negative subgroup of patients with breast cancer.

Cited by 8 publications

References 42 publications

Claudins: New Players in Human Fertility and Reproductive System Cancers

Claudins: New Players in Human Fertility and Reproductive System Cancers

Developmental Expression of Claudins in the Mammary Gland

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

Contact Info

Product

Resources

About