Related Experiment Video

Updated: Aug 29, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Activating mutations in STAT3 and STAT5 differentially affect cellular proliferation and apoptotic resistance in

David R Hodge1, Weihua Xiao, Li Hua Wang

  • 1Laboratory of Molecular Immunoregulation, Cytokine Molecular Mechanisms Section, Center for Cancer Research, The National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.

Cancer Biology & Therapy
|January 17, 2004
PubMed

Insights

Activated STAT factors promote Multiple Myeloma cell proliferation but do not prevent Dexamethasone-induced apoptosis. Cytokine rescue from apoptosis requires PI-3 Kinase, indicating separate mechanisms for proliferation and survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Multiple Myeloma (MM) is a fatal cancer.
  • Dexamethasone is a common MM treatment.
  • Interleukin-6 (IL-6) and Insulin-like Growth Factor-1 (IGF-1) promote MM cell survival and Dexamethasone resistance.

Purpose of the Study:

  • To elucidate the distinct roles of activated STAT factors in MM cell proliferation and resistance to Dexamethasone-induced apoptosis.
  • To differentiate the contributions of upstream signaling pathways from downstream STAT mediators.

Main Methods:

  • Retroviral transduction of MM cells with activated STAT transcription factor constructs.
  • Assessment of cell proliferation under varying serum conditions.
  • Evaluation of Dexamethasone-induced apoptosis.
  • Inhibition studies using PI-3 Kinase and MAP Kinase pathway inhibitors.
  • FAS ligand-induced apoptosis assays.

Main Results:

  • Activated STAT factors enable cytokine-independent MM cell proliferation.
  • Activated STAT factors do not confer resistance to Dexamethasone-induced apoptosis.
  • IL-6 and IGF-1 are required to rescue cells from Dexamethasone-induced apoptosis.
  • Apoptosis resistance mediated by IL-6/IGF-1 is sensitive to PI-3 Kinase inhibitors but not MAP Kinase inhibitors.
  • Activated STAT3 partially rescues cells from FAS ligand-induced apoptosis.

Conclusions:

  • Mechanisms governing proliferation and resistance to apoptosis are distinct in cytokine-dependent MM cells.
  • Activated STAT factors primarily influence proliferation, while apoptosis resistance relies on other pathways like PI-3 Kinase.
  • This research clarifies the complex signaling networks in Multiple Myeloma.

More Related Videos

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...