Role of AKT1 in 17β-estradiol- and insulin-like growth factor I (IGF-I)-dependent proliferation and prevention of apoptosis in MCF-7 breast carcinoma cells

Ahmad, Shakeel; Singh, Nadia Nur; Glazer, Robert I.

doi:10.1016/s0006-2952(99)00125-2

Cited by 155 publications

(119 citation statements)

References 26 publications

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“…It has been reported that activation of MEK/ERK leads to phosphorylation of MITF at serine 73, resulting in its degradation [28,38] . The PI3K⁄Akt pathway plays an important role in cell growth regulation and apoptosis inhibition [39,40] . In addition, activation of the PI3K⁄Akt pathway reduces tyrosinase transcription and melanogenesis in B16F10 cells [17,29] .…”

Section: Discussionmentioning

confidence: 99%

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

Cheng

et al. 2012

Acta Pharmacol Sin

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Aim:To investigate the effect of [6]-shogaol, an active ingredient in ginger, on melanogenesis and the underlying mechanisms. Methods: B16F10 mouse melanoma cells were tested. Cell viability was determined with the MTT assay. Melanin content and tyrosinase activity were analyzed with a spectrophotometer. The protein expression of tyrosinase and microphthalmia associated transcription factor (MITF), as well as phosphorylated or total ERK1/2 and Akt were measured using Western blot.

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Section: Discussionmentioning

confidence: 99%

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

Cheng

et al. 2012

Acta Pharmacol Sin

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“…MMTV-AKT1 was prepared by insertion of a 1.8 kb EcoRI fragment of the human AKT1 cDNA (Ahmad et al, 1999) into the EcoRI site in the plasmid MMTV-SV40-Bssk (kindly provided by Dr Philip Leder). This construct was then digested with SalI and SpeI, and the fragment containing the MMTV promoter, AKT1 sequences and SV40 poly-adenylation signal was isolated by electrophoresis in a 0.8% agarose gel and puri®ed using QIAquick TM (Qiagen).…”

Section: Generation Of Transgenic Micementioning

confidence: 99%

“…AKT2 was ampli®ed in approximately 12% of ovarian cancers and 3% of breast cancers and was associated with a poor prognosis (Bellacosa et al, 1995). AKT1 levels were elevated in virtually all breast cancer cell lines, and its activity was stimulated by IGF-1, estradiol and heregulin (Ahmad et al, 1999;Altiok et al, 1999;Gibson et al, 1999;Liu et al, 1999), resulting in resistance to apoptosis induced by TNFa, Fas ligand or wortmannin (Ahmad et al, 1999;Gibson et al, 1999;Zhou et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Delayed mammary gland involution in MMTV-AKT1 transgenic mice

et al. 2002

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AKT1/protein kinase Ba is a protein-serine/threonine kinase that regulates multiple targets involved in cell survival and cell cycle progression in a variety of cell types including breast cancer cells. To explore the role of Akt1 in mammary gland function and tumorigenesis, transgenic mice were generated that express human AKT1 under the control of the MMTV promoter. Virgin transgenic mice did not exhibit a dominant phenotype, but upon cessation of lactation, a notable delay in involution occurred compared to age-matched nontransgenic mice. The delay in involution coincided with increased hyperplasia as evidenced by an increased number of binucleated epithelial cells and a marked elevation in cyclin D1 expression in mammary epithelium. The delayed involution phenotype corresponded to increased phosphorylation of Thr308 in AKT1 and Ser136 in BAD, but not phosphorylation of Ser21 in GSK-3a. There was no evidence of mammary dysplasia or neoplasia during the lifespan of multiparous transgenic mice. These data suggest that AKT1 is involved in cell survival in the lactating and involuting mammary gland, but that overexpression of AKT1 alone is insu cient to induce transformation.

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“…Platelet-derived growth factor (PDGF) (Klinghoffer et al, 1996), insulin growth factor (IGF) (Duan et al, 1999), and the epidermal growth factor (EGF) family members (Ram and Ethier, 1996;Okano et al, 2000) are among those receptors. Akt-1 has been found in correlation with higher expression of erbB-2 in a panel of breast cancer cell lines (Ahmad et al, 1999). A recent report showed that inhibition of this pathway with a monoclonal antibody against erbB-2 was not restricted to cells that overexpressed erbB-2 but also interfered with heregulin b1 (HRG)-mediated activation in cells with basal levels of the receptor (Liu et al, 1999).…”

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confidence: 99%

Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients

2002

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Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin b1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged 550 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin b1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin b1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer.

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Role of AKT1 in 17β-estradiol- and insulin-like growth factor I (IGF-I)-dependent proliferation and prevention of apoptosis in MCF-7 breast carcinoma cells

Cited by 155 publications

References 26 publications

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

[6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

Delayed mammary gland involution in MMTV-AKT1 transgenic mice

Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients

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