General Information

Introduction:

HMEC stands for Human Mammary Epithelial Cell. The HMEC cell line is a finite lifespan cell line. Many studies are being done to understand how growth, aging, and senescence in HMEC is altered to produce malignant (tumorigenic) cells. Senescence barriers in HMEC 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.

It has been postulated that there are two barriers to immortality in HMEC cells. One is stress-associated, retinoblastoma (Rb) mediated stasis, and the other is telomere dysfunction due to telomere attrition. Inactivating the Rb barrier results in extended life post-stasis cultures, and passing the telomere dysfunction barrier, which causes genomic instability and cell death, results in newly immortal cell cultures. The telomere dystunction barrier can be bypassed by substantial expression of telomerase expression during cell proliferation (mitosis). This is done by de-repressing telomerase. This prevents the shortening of telomeres during cell division, which prevents 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, forever. This is when cells are termed malignant, and finally metastatic. Finite lifespan HMEC are also susceptible to oncogene-induced senescence (OIS). However, once immortality is achieved in HMEC, the cell lines are no longer vulnerable to aging via the OIS mechanism.

Stasis:

Stasis is stress associated. It can be overcome 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.

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.

Links:

An Overview of Growth, Aging, Senescence, and Immortality in our HMEC Culture System

siRNA Delivery – In Vivo Transfection Kits

CRO Pre-clinical Research Services: Xenograft animal models

GLP-compliant Cell Banking services

Generation of Stably Expressing Cell Lines in 28 Days

Stable RNAi Cell Line Generation: Stable Gene Knockdown

In Vivo siRNA Delivery: Tissue-targeted siRNA

Encapsulation of Protein, RNA, mRNA, and DNA Molecules into Liposomes

DNA Damage Response