+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Annexin A8 identifies a subpopulation of transiently quiescent c-kit positive luminal progenitor cells of the ductal mammary epithelium



Annexin A8 identifies a subpopulation of transiently quiescent c-kit positive luminal progenitor cells of the ductal mammary epithelium



Plos one 10(3): E0119718



We have previously shown that Annexin A8 (ANXA8) is strongly associated with the basal-like subgroup of breast cancers, including BRCA1-associated breast cancers, and poor prognosis; while in the mouse mammary gland AnxA8 mRNA is expressed in low-proliferative isolated pubertal mouse mammary ductal epithelium and after enforced involution, but not in isolated highly proliferative terminal end buds (TEB) or during pregnancy. To better understand ANXA8's association with this breast cancer subgroup we established ANXA8's cellular distribution in the mammary gland and ANXA8's effect on cell proliferation. We show that ANXA8 expression in the mouse mammary gland was strong during pre-puberty before the expansion of the rudimentary ductal network and was limited to a distinct subpopulation of ductal luminal epithelial cells but was not detected in TEB or in alveoli during pregnancy. Similarly, during late involution its expression was found in the surviving ductal epithelium, but not in the apoptotic alveoli. Double-immunofluorescence (IF) showed that ANXA8 positive (+ve) cells were ER-alpha negative (-ve) and mostly quiescent, as defined by lack of Ki67 expression during puberty and mid-pregnancy, but not terminally differentiated with ∼15% of ANXA8 +ve cells re-entering the cell cycle at the start of pregnancy (day 4.5). RT-PCR on RNA from FACS-sorted cells and double-IF showed that ANXA8+ve cells were a subpopulation of c-kit +ve luminal progenitor cells, which have recently been identified as the cells of origin of basal-like breast cancers. Over expression of ANXA8 in the mammary epithelial cell line Kim-2 led to a G0/G1 arrest and suppressed Ki67 expression, indicating cell cycle exit. Our data therefore identify ANXA8 as a potential mediator of quiescence in the normal mouse mammary ductal epithelium, while its expression in basal-like breast cancers may be linked to ANXA8's association with their specific cells of origin.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 057201776

Download citation: RISBibTeXText

PMID: 25803307


Related references

FOXC1 is enriched in the mammary luminal progenitor population, but is not necessary for mouse mammary ductal morphogenesis. Biology of Reproduction 89(1): 10, 2013

A tumor promoter-resistant subpopulation of progenitor cells is larger in limbal epithelium than in corneal epithelium. Investigative Ophthalmology & Visual Science 34(8): 2501-2511, 1993

The role of Sox9 in mouse mammary gland development and maintenance of mammary stem and luminal progenitor cells. Bmc Developmental Biology 14: 47, 2014

Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type (clinging ductal carcinoma in situ): A simulator of normal mammary epithelium. Cancer 88(9): 2072-2081, 2000

The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Research 68(19): 7711-7717, 2008

The 9a5 antigen identifies early t and b lineage cells and a subpopulation of mature cd4 positive t cells. FASEB Journal 4(7): A1731, 1990

Modeling luminal breast cancer heterogeneity: combination therapy to suppress a hormone receptor-negative, cytokeratin 5-positive subpopulation in luminal disease. Breast Cancer Research 16(4): 418, 2014

Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34(+)CD38(-) progenitor cells from patients with acute myeloid leukemia. Blood 97(12): 3882-3889, 2001

Notch3 marks clonogenic mammary luminal progenitor cells in vivo. Journal of Cell Biology 203(1): 47-56, 2013

Differential expression of annexin I in human mammary ductal epithelial cells in normal and benign and malignant breast tissues. Clinical & Experimental Metastasis. 15(2): 151-156, 1997

Low CD38 Identifies Progenitor-like Inflammation-Associated Luminal Cells that Can Initiate Human Prostate Cancer and Predict Poor Outcome. Cell Reports 17(10): 2596-2606, 2016

The 9a5 antigen identifies early myeloid t and b cell lineages and a subpopulation of mature cd4 positive t cells. Journal of Cellular Biochemistry Suppl. (16 Part C): 61, 1992

Cytokeratin 5 positive cells represent a steroid receptor negative and therapy resistant subpopulation in luminal breast cancers. Breast Cancer Research and Treatment 128(1): 45-55, 2011