Lymphangioleiomyomatosis and TSC2-/- cells.
The cells comprising pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipomas (AMLs) are heterogeneous, with variable mixtures of cells exhibiting differentiation towards smooth muscle, fat, and vessels. Cells grown from LAM and AMLs have likewise tended to be heterogeneous. The discovery that LAM and AMLs contain cells with mutations in the TSC1 or TSC2 genes is allowing investigators to discriminate between "two-hit" cells and neighboring cells, providing insights into disease pathogenesis. In rare cases, it has been possible to derive cells from human tumors, including AMLs and TSC skin tumors that are highly enriched for TSC2(-/-) cells. Cells derived from an Eker rat uterine leiomyoma (ELT3 cells) are Tsc2-null and these have been used in a rodent cell models for LAM. Further improvements in the ability to reliably grow well-characterized TSC2(-/-) cells from human tumors are critical to developing in vitro and in vivo model systems for studies of LAM pathogenesis and treatment.
Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. tdarling@usuhs.mil
Thomas N
TN
Darling
Gustavo
G
Pacheco-Rodriguez
Alfredo
A
Gorio
Elena
E
Lesma
Cheryl
C
Walker
Joel
J
Moss
D000818:Animals; D004195:Disease Models, Animal; D006720:Homozygote; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D014402:Tuberous Sclerosis / Q000378:metabolism / Q000473:pathology*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C000624653:TSC2 protein, human; C000624654:Tsc2 protein, mouse; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins