The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells

Lu, Yiling; Yang, Lin; LaPushin, Ruth; Cuevas, Bruce D.; Fang, Xianjun; Yu, Shuang; Davies, Michael A.; Khan, Humera; Furui, Tatsuro; Mao, Muling; Zinner, Ralph; Hung, Mien‐Chie; Steck, Peter A.; Siminovitch, Kathy; Mills, Gordon B.

doi:10.1038/sj.onc.1203183

Cited by 275 publications

(209 citation statements)

References 37 publications

(39 reference statements)

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“…A putative tumor suppressor gene, PTEN, was identified at 10q23 and is thought to play an important role in the control of cell proliferation, apoptosis, differentiation, 23,24 and break cell cycle progression by inhibiting the phosphatidylinositol 3 0 -kinase pathway. 25,26 PTEN was mutated or deleted homozygously in glioma, endometrial, and breast carcinoma tumors.…”

Section: Discussionmentioning

confidence: 99%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n ¼ 23), large cell neuroendocrine carcinoma (n ¼ 17), and classic large cell carcinoma (n ¼ 12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (Po0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P ¼ 0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P ¼ 0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P ¼ 0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.

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Section: Discussionmentioning

confidence: 99%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

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“…Similar to what this study found for ERK1/2 activity, the activation status of the PI3K/AKT pathway may influence responses to inhibitors. For example, Moasser et al (2001) found that MDA-MB-468 cells were relatively resistant to the tyrosine kinase inhibitor ZD1839, and this was attributed to the high basal AKT activity, resulting from deletion of the PTEN tumour suppressor (Lu et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells

et al. 2004

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One of the major targets for breast cancer therapy is the epidermal growth factor receptor (EGFR) and related receptors, which signal via different signal transduction pathways including the mitogen-activated protein kinase (MAPK) pathway. This study determined whether there is a correlation between EGFR/HER2 status and MAPK (ERK1/2) phosphorylation in breast cancer cells, and how this affects the response to an inhibitor of the receptors. Expression of EGFR, HER2 and phosphorylated ERK1/2 were measured by immunoblotting in a panel of breast cancer cell lines. Several lines expressed high levels of pERK1/2, with no obvious correlation with the level of EGFR/HER2. The EGFR tyrosine kinase inhibitor PKI166 inhibited growth and induced apoptosis in some cells with high levels of growth factor receptors (MDA-MB-468, SUM149, SKBR3), but was less effective in cells that also had high basal ERK1/2 activity (MDA-MB-231). The combination of an inhibitor of MAPK signalling (U0126) and PKI166 produced significantly more inhibition and apoptosis than either agent alone. This suggests that constitutive activation of the MAPK pathway may bypass inhibition of EGFR/HER2 tyrosine kinases, and lead to insensitivity to agents targeting the receptors. However, inhibiting both EGFR/ HER2 and MAPK signalling can result in significant growth inhibition and apoptosis of EGFR-expressing breast cancer cells.

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“…In this respect, inactivation of PTEN, the major phosphatase controlling PI3K/Akt signaling, is commonly observed in tumors, and contributes to the anchorage independence of these cells. 103,104 Activation of Akt via overexpression of integrin-linked kinase has a similar effect. 105 While this discussion in not comprehensive, these interactions along the Akt signaling axis provide a mechanism to explain how ligated integrins can mediate signaling events which oppose cell death induced by a variety of proapoptotic stimuli, including unligated integrins.…”

Section: Signaling Cascades and The Integrin Rheostatmentioning

confidence: 92%

Integrins as a distinct subtype of dependence receptors

Stupack

2005

Cell Death Differ

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In the absence of their cognate ligand, dependence receptors trigger programmed cell death. This function is the defining feature of dependence receptors, which include members of several different protein families. The integrins are a family of heterodimeric receptors for extracellular matrix (ECM) proteins, mediating cell anchorage and migration. Integrins share characteristics with dependence receptors, and integrin binding to substrate ECM ligands is essential for cell survival. Although integrins do not conform in all characteristics to the established definitions of dependence receptors, alterations in the expression of integrins and their ligands during physiological and pathological events, such as wound healing, angiogenesis and tumorigenesis, do regulate cell fate in a ligand-dependent manner. This biosensory function of integrins fits well with our current concept of dependence receptor action, and thus integrins may rightly be considered to comprise a distinct subclass of dependence receptor.

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The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells

Cited by 275 publications

References 37 publications

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells

Integrins as a distinct subtype of dependence receptors

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