Expression Profiling of Purified Normal Human Luminal and Myoepithelial Breast Cells

Abstract

The normal duct-lobular system of the breast is lined by two epithelial cell types, inner luminal secretory cells and outer contractile myoepithelial cells. We have generated comprehensive expression profiles of the two normal cell types, using immunomagnetic cell separation and gene expression microarray analysis. The cell-type specificity was confirmed at the protein level by immunohistochemistry in normal breast tissue. New prognostic markers for survival were identified when the luminal-and myoepithelial-specific molecules were evaluated on breast tumor tissue microarrays. Nuclear expression of luminal epithelial marker galectin 3 correlated with a shorter overall survival in these patients, and the expression of SPARC (osteonectin), a myoepithelial marker, was an independent marker of poor prognosis in breast cancers as a whole. These data provide a framework for the interpretation of breast cancer molecular profiling experiments, the identification of potential new diagnostic markers, and development of novel indicators of prognosis.

A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines

“…Basal specific genes in breast cancer cell lines included two isoforms of caveolin (CAV1 and CAV2), as well as VIM, LY6K and PRNP as previously described [28][29][30]. These genes correlate well with our previous reports of oestrogen responsive genes in primary breast cancers [19] and with genes associated with the basal-like phenotype of breast epithelial cells [26] and primary basal-like breast cancers [3]. The complete list of significant genes differentially expressed in luminal and basal-like cells are shown in Supplementary Tables S4A and S4B.…”

“…In fact, group 1 is remarkably similar to that described by Neve et al [4] as a ''luminal'' group. Group 2 was comprised of cell lines with variable morphology, which expressed genes usually found in basal/ myoepithelial cells of the normal breast and primary basallike breast cancers [5,6,26]. It should be noted that group 2 comprised two separate subgroups, the first encompassing normal endothelial cells, fibroblasts, luminal epithelial cells, myoepithelial cells, HMECs and MCF12A, the HER2 amplified cell line MDA-MB-453 and the carcinosarcoma/ metaplastic breast cancer cell line Hs578T.…”

Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases

“…However, as SPARC has the potential to function both as a tumor promoter and tumor suppressor, decreasing SPARC expression may not be beneficial for all tumor types or stages. For example, SPARC induces apoptosis in ovarian cancer cells (Yiu et al, 2001) and inhibits proliferation and metastasis of breast cancer cells (Koblinski et al, 2005), but breast tumor expression of SPARC is linked to increased patient metastases and poor patient survival (Jones et al, 2004;Watkins et al, 2005). When we overexpressed SPARC in HeLa cells or a genetically engineered human breast cancer model (HMEC), SPARC-expressing cells suffered a dramatic inhibition of tumor formation when implanted into immunocompromised rodents (data not shown).…”

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

“…For example, distinguishing ductal carcinoma in situ (DCIS) vs invasive ductal carcinoma, radial scar vs infiltrating tubular carcinoma, cancerisation of sclerosing adenosis by DCIS mimicking invasive breast carcinoma, adenoid cystic carcinoma vs collagenous spherulosis or cribriform DCIS, papillary carcinoma vs papilloma, and nipple adenoma vs invasive ductal carcinoma. [18][19][20][21] In recent years, several myoepithelial markers have been described, most of them either related to the basal nature of myoepithelial cells or to the smooth muscle apparatus of these cells. [18][19][20][21][22] However, the development of novel myoepithelial markers is not only important for diagnostic purposes but also for prognostication.…”

“…[18][19][20][21] In recent years, several myoepithelial markers have been described, most of them either related to the basal nature of myoepithelial cells or to the smooth muscle apparatus of these cells. [18][19][20][21][22] However, the development of novel myoepithelial markers is not only important for diagnostic purposes but also for prognostication. There are several lines of evidence to suggest that highgrade breast carcinomas expressing basal/myoepithelial markers have distinct pathological features, expression profiles and, most importantly, clinical behaviour when compared to high-grade breast carcinomas devoid of basal-like differentiation.…”