Limits...
Sonic hedgehog opposes epithelial cell cycle arrest.

Fan H, Khavari PA - J. Cell Biol. (1999)

Bottom Line: Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo.Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity.In addition, Shh blocks p21(CIP1/WAF1)-induced growth arrest.

View Article: PubMed Central - PubMed

Affiliation: VA Palo Alto Health Care System, Palo Alto, California 94304, USA.

ABSTRACT
Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity. In addition, Shh blocks p21(CIP1/WAF1)-induced growth arrest. These data indicate that Shh promotes neoplasia by opposing normal stimuli for epithelial cell cycle arrest.

Show MeSH

Related in: MedlinePlus

Shh-expressing cells fail to appropriately exit S and G2/M phases in response to calcium-induced differentiation. Cell cycle distribution was determined in cells in low calcium growth media and in cells undergoing calcium-induced differentiation in vitro via elevation of the media calcium concentration to 1.5 mM. Shh and GFP control cells were analyzed for DNA content via flow cytometry. (a) Control, growth media. (b) Shh[+], growth media. (c) Control, 1.5 mM calcium. (d) Shh[+] 1.5 mM calcium. Representative plots are shown; accompanying percentage figures represent the averages of three independent transductions and flow cytometric analyses for Shh and controls ± SEM
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2164980&req=5

Figure 2: Shh-expressing cells fail to appropriately exit S and G2/M phases in response to calcium-induced differentiation. Cell cycle distribution was determined in cells in low calcium growth media and in cells undergoing calcium-induced differentiation in vitro via elevation of the media calcium concentration to 1.5 mM. Shh and GFP control cells were analyzed for DNA content via flow cytometry. (a) Control, growth media. (b) Shh[+], growth media. (c) Control, 1.5 mM calcium. (d) Shh[+] 1.5 mM calcium. Representative plots are shown; accompanying percentage figures represent the averages of three independent transductions and flow cytometric analyses for Shh and controls ± SEM

Mentions: To determine if Shh confers a resistance to differentiation-associated cell cycle arrest, Shh[+] and control cells were grown to confluence in vitro then media calcium concentration was raised to 1.5 mM in a process that recapitulates features of differentiation seen in vivo, including cell cycle arrest and activation of certain terminal differentiation genes 18. Cell cycle distribution was analyzed both before differentiation stimuli and 48 h after addition of calcium. Shh[+] and control cells are indistinguishable under low calcium conditions promoting cellular proliferation, with the majority of cells in G2/M and S phase (Fig. 2). As anticipated, the addition of calcium induces exit of the majority of normal control cells into G0/G1. Whereas Shh[+] cells alter their cell cycle distribution in response to calcium, instead of redistributing to G0/G1 these cells are disproportionately in G2/M and S phase (Fig. 2). These findings indicate Shh opposes cell cycle inhibitory effects of a primary in vitro stimulus for epithelial differentiation.


Sonic hedgehog opposes epithelial cell cycle arrest.

Fan H, Khavari PA - J. Cell Biol. (1999)

Shh-expressing cells fail to appropriately exit S and G2/M phases in response to calcium-induced differentiation. Cell cycle distribution was determined in cells in low calcium growth media and in cells undergoing calcium-induced differentiation in vitro via elevation of the media calcium concentration to 1.5 mM. Shh and GFP control cells were analyzed for DNA content via flow cytometry. (a) Control, growth media. (b) Shh[+], growth media. (c) Control, 1.5 mM calcium. (d) Shh[+] 1.5 mM calcium. Representative plots are shown; accompanying percentage figures represent the averages of three independent transductions and flow cytometric analyses for Shh and controls ± SEM
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2164980&req=5

Figure 2: Shh-expressing cells fail to appropriately exit S and G2/M phases in response to calcium-induced differentiation. Cell cycle distribution was determined in cells in low calcium growth media and in cells undergoing calcium-induced differentiation in vitro via elevation of the media calcium concentration to 1.5 mM. Shh and GFP control cells were analyzed for DNA content via flow cytometry. (a) Control, growth media. (b) Shh[+], growth media. (c) Control, 1.5 mM calcium. (d) Shh[+] 1.5 mM calcium. Representative plots are shown; accompanying percentage figures represent the averages of three independent transductions and flow cytometric analyses for Shh and controls ± SEM
Mentions: To determine if Shh confers a resistance to differentiation-associated cell cycle arrest, Shh[+] and control cells were grown to confluence in vitro then media calcium concentration was raised to 1.5 mM in a process that recapitulates features of differentiation seen in vivo, including cell cycle arrest and activation of certain terminal differentiation genes 18. Cell cycle distribution was analyzed both before differentiation stimuli and 48 h after addition of calcium. Shh[+] and control cells are indistinguishable under low calcium conditions promoting cellular proliferation, with the majority of cells in G2/M and S phase (Fig. 2). As anticipated, the addition of calcium induces exit of the majority of normal control cells into G0/G1. Whereas Shh[+] cells alter their cell cycle distribution in response to calcium, instead of redistributing to G0/G1 these cells are disproportionately in G2/M and S phase (Fig. 2). These findings indicate Shh opposes cell cycle inhibitory effects of a primary in vitro stimulus for epithelial differentiation.

Bottom Line: Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo.Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity.In addition, Shh blocks p21(CIP1/WAF1)-induced growth arrest.

View Article: PubMed Central - PubMed

Affiliation: VA Palo Alto Health Care System, Palo Alto, California 94304, USA.

ABSTRACT
Stratified epithelium displays an equilibrium between proliferation and cell cycle arrest, a balance that is disrupted in basal cell carcinoma (BCC). Sonic hedgehog (Shh) pathway activation appears sufficient to induce BCC, however, the way it does so is unknown. Shh-induced epidermal hyperplasia is accompanied by continued cell proliferation in normally growth arrested suprabasal cells in vivo. Shh-expressing cells fail to exit S and G2/M phases in response to calcium-induced differentiation and also resist exhaustion of replicative growth capacity. In addition, Shh blocks p21(CIP1/WAF1)-induced growth arrest. These data indicate that Shh promotes neoplasia by opposing normal stimuli for epithelial cell cycle arrest.

Show MeSH
Related in: MedlinePlus