General Information

HMEC Introduction

HMEC stands for Human Mammary Epithelial Cell. The HMEC cell line is naturally non-immortal and used in studies to understand how growth, aging and senescence is altered to produce malignant (tumorigenic) cells. Senescence barriers in HMEC are pathway checkpoints that function to stop the development of tumorigenic cells. Studies using HMEC can give insight into pathways to cellular aging and the development of malignant cell types in vivo, and possibly into therapeutic interventions for breast carcinogenesis.

HMEC Immortality

It has been postulated that there are two barriers to overcome to achieve immortality in HMEC cells. The first barrier is a stress-associated stage called retinoblastoma (Rb) mediated stasis. The result of inactivating the Rb barrier is extended post-stasis cultures. The second barrier is telomere dysfunction that can result in genomic instability, cell death and a newly immortal cell cultures. The telomere dysfunction barrier can be bypassed by substantial expression of telomerase during cell proliferation (mitosis), as done by de-repressing telomerase. This prevents the shortening of telomeres during cell division, thus, preventing cell death after a finite number of divisions. This is characteristic of many immortal cell lines, such as the HeLa cell line, which naturally display substantial telomerase activity during cell mitosis. HMEC cells are fully immortal once cell culture has sufficient telomerase activity to maintain stable telomeres.

HMEC cells are not naturally immortal and any genetic mutations during proliferation of the cells prior to immortalization can lead to the incorporation those accumulated abnormalities. Thus, it is vital cells are immortalized as close to initial culture as possible, at the lowest passage number, to lessen the amount of instability incorporated in the cellular genome.

HMEC Stasis

Cell stasis is the ability of cells to overcome replicative senescence.  Cells can overcome the senescence barrier in cell culture by altering pathways governing Rb, either genetically or by other means. Stasis is also telomere length independent. This means reactivating telomerase during cell proliferation has no effect on stasis and does not help to overcome it. Overcoming stasis may be correlated with some types of cancer and has been linked with hyperplasia, or uncharacteristic cell proliferation in vivo.

HMEC Telomere Dysfunction Due to Telomere Attrition

This is the second barrier to malignancy and occurs only in cells that have already bypassed stasis due to ongoing proliferation. Each time a cell divides, genomic telomeres are shortened, in the absence of telomerase activity. At a critically short level, genomic instability and the DNA damage response (DDR) is elicited. The cellular response to damage often results in the initiation of either a repair pathway, commencement of transcription, cell cycle checkpoint activation, or apoptosis.

Telomere attrition can be overcome by substantial telomerase expression during mitosis. Surpassing telomere dysfunction may result in Ductal carcinoma in situ (DCIS), the most common type of non-invasive breast cancer. This cancer is characterized by short telomeres, genomic instability, and telomerase reactivation.

HMEC Oncogene-Induced Senescence

As the name suggests, oncogene-induced senescence (OIS) is the ability of a cell to inhibit progression of cells into malignant tumors upon activation of an oncogene. Some proposed oncogenes include p53, Ras, PTEN, NF1, Rb, etc. There are observations in literature that capture the initial proliferative burst of growth followed by senescence upon activation of these key pathways. It is proposed that the OIS mechanism suppresses the development of a tumor in vivo by stopping the progression of benign hyperplasia. However, additional gene mutations can likely trigger progression of tumor growth.

Finite lifespan HMEC cells are susceptible to oncogene-induced senescence (OIS). However, once immortality is achieved, HMEC cells are no longer vulnerable to aging via the OIS mechanism.


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