Disease relevance of Contact Inhibition

• TLS/FUS-CHOP type II protein showed transforming activity, as evidenced by loss of contact inhibition of growth, anchorage-independent growth in soft agar, and tumor formation in nude mice, showing typical histological features of myxoid liposarcoma seen in humans [1].
• In glioma cells, the constitutive presence of FGF-2 in the nucleus may promote proliferation that is insensitive to cell contact inhibition [2].
• Consequently, the phosporylation level of the retinoblastoma (Rb) protein remained high in these cells, whereas there was no phosporylated Rb in VHL (+) cells under the contact inhibition [3].
• Interferon-beta (IFN-beta) used as a biological response modifier can cause a wide array of effects, including the restoration of contact inhibition in HT1080 fibrosarcoma cells normally lacking this control [4].
• Protocadherin LKC, a new candidate for a tumor suppressor of colon and liver cancers, its association with contact inhibition of cell proliferation [5].

High impact information on Contact Inhibition

• We demonstrate that active repression by Rb-E2F mediates the G1 arrest triggered by TGFbeta, p16INK4a, and contact inhibition [6].
• In Rat-1 cells, LMP expression often led to loss of contact inhibition and anchorage-independent growth in soft agar [7].
• We found that merlin mediates contact inhibition of growth through signals from the extracellular matrix [8].
• p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest [9].
• Treatment with nicotine or NNK attenuated apoptosis caused by etoposide, ultraviolet irradiation, or hydrogen peroxide and partially induced a transformed phenotype manifest as loss of contact inhibition and loss of dependence on exogenous growth factors or adherence to ECM [10].

Chemical compound and disease context of Contact Inhibition

• A mechanism for the loss of contact inhibition is discussed based on the over-expression of CSL ligands in C6 glioblastoma cells relative to normal cells [11].
• CONCLUSIONS: These findings suggest that oxidative stress-induced activation of mu-calpain causes proteolysis of merlin conceivably to impair cell adhesion and/or contact inhibition of meningioma cells [12].
• The growth of cell cultures from cystathionine synthetase deficient individuals with homocystinuria is characterized by abnormal contact inhibition and production of an aggregated proteoglycan matrix which binds excess sulfate [13].
• Untransformed rat kidney cells transformed with the Kirsten murine sarcoma virus exhibit a low cyclic AMP content, rapid growth rate, and a loss of contact inhibition [14].

Biological context of Contact Inhibition

• Herein, we report that expression of GlcNAc-TV in Mv1Lu cells, an immortalized lung epithelial cell line results in loss of contact-inhibition of cell growth, an effect that was blocked by swainsonine, an inhibitor of Golgi processing enzyme alpha-mannosidase II [15].
• Our results suggest that upregulation of caveolin-1 may be important in mediating contact inhibition and negatively regulating the activation state of the p42/44 MAP kinase cascade [16].
• Pak1 and PIX regulate contact inhibition during epithelial wound healing [17].
• A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer [18].
• Cells that did not show contact inhibition of growth had a functional p53 regardless of cell density [19].

Anatomical context of Contact Inhibition

• Introduction of activated p21-activated kinase (PAK) is sufficient to release primary endothelial cells from contact inhibition of growth [20].
• Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane [20].
• The contact inhibition observed in the alpha5 myoblasts is mediated by N-cadherin, whose expression is upregulated more than fivefold [21].
• Blot-hybridization analysis revealed that RNA levels corresponding to the three repressed genes decreased when HT1080 cells were treated with IFN or when proliferation of normal CUA foreskin fibroblast cells became naturally arrested by contact inhibition [22].
• In this report, we show that T-cadherin expression increased during primary astrocyte physiologic growth arrest in response to contact inhibition and serum starvation in vitro, suggesting a function for T-cadherin in astrocyte growth regulation [23].

Associations of Contact Inhibition with chemical compounds

• These data suggested the restoration of contact inhibition (topoinhibition) to L-929 cells treated with retinoic acid [24].
• Integrin and cadherin synergy regulates contact inhibition of migration and motile activity [21].
• Removal of zinc chloride from the medium resulted in reduced expression of T antigen and a change in the appearance of the cells to a more bipolar shape, although they still did not exhibit contact inhibition and maintained a doubling time of 20 h [25].
• When contact inhibition in endothelial monolayers was locally released by wounding, and LDL was present, only cells released from contact inhibition accumulated LDL cholesterol [26].
• At the cellular level, restoration of tuberin expression caused morphological changes characterized by enlargement of the cells and increased contact inhibition [27].

Gene context of Contact Inhibition

• Overall the data indicate that VE-cadherin-beta-catenin complex participates in contact inhibition of VEGF signaling [28].
• Since these cells were noncycling, we examined whether the ectopic expression of any cyclin could override contact inhibition of growth and restore p53 transactivation function [19].
• Ectopic expression of S100B in clone 6 cells restores contact inhibition of growth at 37.5 degreesC, which also correlates with nuclear accumulation of the wild-type p53Val135 conformational species [29].
• They induced morphological alterations and slightly accelerated proliferation in NIH 3T3 fibroblasts but were not tumorigenic in mice and behaved like wild-type Raf-1 in transformation assays measuring loss of contact inhibition or anchorage-independent growth [30].
• Growth arrest of normal diploid cells by contact inhibition resulted in an induction of p27(kip1) and reduction of CDK2 levels [31].

Analytical, diagnostic and therapeutic context of Contact Inhibition

• Northern blot analysis confirmed that the cyclin A mRNA steady-state abundance decreased dramatically in response to a 24-hr TGF-beta 1 treatment and also in response to cell cycle arrest caused by contact inhibition [32].
• The cells demonstrated lack of contact inhibition in culture, were slightly positive in acid phosphatase tests, and reacted positively with cytomegalovirus (CMV)-immune sera in indirect immunofluorescence (IF) tests [33].

References