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The characterization of cell line crl-2335 as a Basal-like breast carcinoma model.

ABSTRACT: Basal-like breast cancer has been reported to be the most aggressive and deadly carcinoma sub-type. Patients diagnosed with this subtype have a less than 50% five-year survival. In addition, many studies have reported that this sub-type is more prevalent in specific ethnic groups and is believed to be a key factor that drives certain ethnic disparities in mortality. In order to effectively study this sub-type and determine unique gene expression and biochemical pathways which sustain this cancer's growth, we sought to identify human breast cancer cell lines that represent a model for the basal-like subtype. Here, we report our findings which indicate the African American cell line CRL-2335 is a true representative of basal-like breast carcinoma.

SUBMITTER: Hill Neves LA

PROVIDER: S-EPMC3091405 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The characterization of cell line crl-2335 as a Basal-like breast carcinoma model.

Hill Neves Lori A LA Ingram Lishann L Davis Melissa B MB

Breast cancer : basic and clinical research 20110427

Basal-like breast cancer has been reported to be the most aggressive and deadly carcinoma sub-type. Patients diagnosed with this subtype have a less than 50% five-year survival. In addition, many studies have reported that this sub-type is more prevalent in specific ethnic groups and is believed to be a key factor that drives certain ethnic disparities in mortality. In order to effectively study this sub-type and determine unique gene expression and biochemical pathways which sustain this cancer ...[more]

PMID: 21603256

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Project description:The phenotypic diversity of breast carcinoma may be explained by the existence of a sub-population of breast cancer cells, endowed with stem cell-like properties and gene expression profiles, able to differentiate along different pathways. A stem cell-like population of CD44(+)CD24(-/low) breast cancer cells was originally identified using cells from metastatic pleural effusions of breast carcinoma patients. We have previously reported that upon in vitro culture as mammospheres under stem cell-like conditions, human MA-11 breast carcinoma cells acquired increased tumorigenicity and lost CD24 expression compared with the parental cell line. We now report that upon passage of MA-11 mammospheres into serum-supplemented cultures, CD24 expression was restored; the rapid increase in CD24 expression was consistent with up-regulation of the antigen, and not with in vitro selection of CD24(+) cells. In tumors derived from subcutaneous injection of MA-11 mammospheres in athymic nude mice, 76.1+/-9.7% of cells expressed CD24, vs. 0.5+/-1% in MA-11 cells dissociated from mammospheres before injection. The tumorigenicity of sorted CD44(+)CD24(-) and CD44(+)CD24(high) MA-11 cells was equal. Single cell-sorted CD24(-) and CD24(high) MA-11 gave rise in vitro to cell populations with heterogeneous CD24 expression. Also, subcutaneous tumors derived from sorted CD24(-) sub-populations and single-cell clones had levels of CD24 expression similar to the unsorted cells. To investigate whether the high expression of CD24 contributed to the tumorigenic potential of MA-11 cells, we silenced CD24 by shRNA. CD24 silencing (95%) resulted in no difference in tumorigenicity upon s.c. injection in athymic nude mice compared with mock-transduced MA-11 cells. Since CD24 silencing was maintained in vivo, our data suggest that the level of expression of CD24 is associated with but does not contribute to tumorigenicity. We then compared the molecular profile of the mammospheres with the adherent cell fraction. Gene expression profiling revealed that the increased tumorigenicity of MA-11 mammospheres was associated with changes in 10 signal transduction pathways, including MAP kinase, Notch and Wnt, and increased expression of aldehyde dehydrogenase, a cancer-initiating cell-associated marker. Our data demonstrate that (i) the level of CD24 expression is neither a stable feature of mammosphere-forming cells nor confers tumorigenic potential to MA-11 cells; (ii) cancer-initiating cell-enriched MA-11 mammospheres have activated specific signal transduction pathways, potential targets for anti-breast cancer therapy.

Dataset Information

The characterization of cell line crl-2335 as a Basal-like breast carcinoma model.

Publications

The characterization of cell line crl-2335 as a Basal-like breast carcinoma model.

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