Density-dependent modulation of synthesis of keratins 1 and 10 in the human keratinocyte line HACAT and in ras-transfected tumorigenic clones.

  title={Density-dependent modulation of synthesis of keratins 1 and 10 in the human keratinocyte line HACAT and in ras-transfected tumorigenic clones.},
  author={Catherine Ryle and Dirk Breitkreutz and Hans J{\"u}rgen Stark and I. M. Leigh and Peter M. Steinert and Dennis R. Roop and Norbert E Fusenig},
  journal={Differentiation; research in biological diversity},
  volume={40 1},
The spontaneous human keratinocyte line HaCaT and c-Ha-ras oncogene-transfected cell clones are capable of expressing an unusually broad spectrum of keratins, not observed so far in epithelial cells. This expression is, however, strongly modulated by environmental conditions, including cell density. Both cells of the nontumorigenic HaCaT line and the tumorigenic HaCaT-ras clones, I-7 and II-3 (giving rise to benign and malignant tumors, respectively), constitutively expressed the keratins K5… 

Epidermal morphogenesis and keratin expression in c-Ha-ras-transfected tumorigenic clones of the human HaCaT cell line.

Several tumorigenic (benign and malignant) clones have been raised from the human epidermal cell line HaCaT after transfection with the c-Ha-ras oncogene (val 12) (P. Boukamp et al., Cancer Res., 50:

Differential modulation of epidermal keratinization in immortalized (HaCaT) and tumorigenic human skin keratinocytes (HaCaT-ras) by retinoic acid and extracellular Ca2+.

In vitro results demonstrate that, in spite of some differences in RA sensitivity, virtually all clones possess the epidermal differentiation repertoir which is regulated according to the same principles, and confirms in vivo data that differentiation potential is not inversely related to the state of transformation or tumorigenicity.

Up-modulation of the expression of functional keratinocyte growth factor receptors induced by high cell density in the human keratinocyte HaCaT cell line.

  • A. CaponeV. Visco M. Torrisi
  • Biology
    Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
  • 2000
The process of modulation of the expression of KGFRs in the human keratinocytes cell line HaCaT, widely used as a model to study keratinocyte differentiation, showed that cell differentiation and stratification induced by confluence and high cell density correlated with an increase in KG FR expression.

Serum factors regulate the expression of the proliferation-related genes α5 integrin and keratin 1, but not keratin 10, in HaCaT keratinocytes

Findings indicate that ·5 integrin and K1/K10 are involved in the regulation of HaCaT proliferation and differentiation, as in normal keratinocytes, however, Ha CaT cells are different from normal Keratinocytes in their ability to lose K1 /K10 expression.

c-Ha-ras oncogene expression in immortalized human keratinocytes (HaCaT) alters growth potential in vivo but lacks correlation with malignancy.

Spontaneously immortalized human skin keratinocytes (HaCaT) were transfected with the c-Ha-ras (EJ) oncogene via a plasmid construct which also contained the selectable neomycin gene. Clones were

Human Keratinocyte Cell Lines

HaCaT and derived cell lines provide readily available cell culture models and might offer useful alternatives to primary or low-passaged normal keratinocytes and some promising applications are: testing and detection of growth and differentiation factors, synthesis of differentiation products and epidermis-derived factors and introduction of exogenous genes or subgenomic regulatory elements.

c-Haras Oncogene Expression in Immortalized Human Keratinocytes ( HaCaT ) Alters Growth Potential in Vivo but Lacks Correlation with Malignancy 1

Exposure to the cellular Ha-rav oncogene significantly altered growth regulation, resulting in varying degrees of growth potential in vivo, ranging from benign to malignant tumors, however, no direct correlation was seen between high levels of p21 expression and malignant growth.

Impact of Bcl-2 and Ha-ras on keratinocytes in organotypic culture.

Organotypic keratinocyte culture represents a valuable in vitro system to evaluate the impact of individual molecular genetic alterations on the coordinate regulation of cell proliferation, differentiation, and cell death.

Expression of 38-kD cell-surface glycoprotein in transformed human keratinocyte cell lines, basal cell carcinomas, and epithelial germs.

The immunohistologic data suggest that gp 38 is preferentially expressed by epidermal cells which lack squamous and pilosebaceous differentiation, and which is also found in primary epithelial germs of fetal skin, secondary germ cells of the telogenic hair follicle and secretory tubules of sweat glands.



Regulated expression of differentiation-associated keratins in cultured epidermal cells detected by monospecific antibodies to unique peptides of mouse epidermal keratins.

By applying single-and double-label immunofluorescence analysis, the expression of keratin peptides was analyzed in cultured keratinocytes maintained in the basal or suprabasal cell phenotypes and indicated that virtually all K10- positive cells also expressed K1, while only about one-half of the K1-positive cells expressed K10.

Retinoids as important regulators of terminal differentiation: examining keratin expression in individual epidermal cells at various stages of keratinization

Interestingly, K13 expression correlated well with the gradient of retinoid-mediated disruptions of intercellular interactions in the culture, suggesting that K13 induction may in some way relate to the reduction in either the number or the strength of desmosomal contacts between suprabasal cells of stratified squamous epithelial tissues.

Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A.

The findings suggest that the altered patterns of keratins observed for some tissues upon malignant transformation arise from a complex mixture of intracellular changes in the differentiative pathway in addition toChanges in the responsiveness of cells to extracellular regulators of keratin gene expression.

Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells

Keratin expression data suggest that the acidic 55K and basic 64K keratins represent markers for an advanced stage of corneal epithelial differentiation.

Environmental induction of differentiation-specific keratins in malignant mouse keratinocyte lines.

While cell differentiation appeared virtually normal, the progressive disturbances in tissue differentiation indicate important changes in the responsiveness of these malignant keratinocytes to environmental conditions.

Keratin classes: molecular markers for different types of epithelial differentiation.

Findings suggest that specific keratin classes, as defined by monoclonal antibodies, may serve as useful markers for different types of epithelial differentiation (simple versus stratified, keratinized versus nonkeratinized).

Growth and differentiation characteristics of transformed keratinocytes from mouse and human skin in vitro and in vivo.

The transplantation assay for studying cellular invasiveness not only improves the sensitivity of in vivo malignancy tests but has also proved to be a valuable model system for elucidating the modulation of differentiation by external influences.

Measurement of the rate of epidermal terminal differentiation: expression of involucrin by S-phase keratinocytes in culture and in psoriatic plaques.

The experiments show that temporal separation of proliferation and terminal differentiation is not obligatory, and thus, the kinetic organization of epidermis may be less rigid than some models imply.

Differentiation specific functions in cultured and transplanted mouse keratinocytes: environmental influences on ultrastructure and keratin expression.

Almost complete restoration of epidermal function was achieved after transplantation of PEC onto adult syngeneic mice and, although keratinocytes in primary culture differ considerably from those in vivo, they have not irreversibly lost the capacity for complete differentiation.

Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes

The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes, implying that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases.