Signal Transducer and Activator of Transcription (STAT)-5A and STAT5B Differentially Regulate Human Mammary Carcinoma Cell Behavior

Abstract Increased activation of signal transducer and activator of transcription (STAT)-5 has been reported in various malignancies including mammary carcinoma. However, it is only recently that potentially distinct roles of STAT5A and STAT5B in neoplasia have begun to emerge. Herein we systematically delineate the functions of STAT5A and STAT5B in human mammary carcinoma cell lines MCF-7 and T47D. Forced expression of constitutively active (CA) STAT5A enhanced both survival and anchorage-independent growth of human mammary carcinoma cells but concordantly suppressed cell motility as revealed in colony scattering, cell migration, and invasion assays. In contrast, forced expression of CA STAT5B exhibited lower potency than CA STAT5A in enhancing survival and anchorage-independent growth of mammary carcinoma cells and exerted no effects on cell motility. Differential expression of genes that regulate cellular survival and motility was concomitantly observed on forced expression of CA STAT5A or CA STAT5B. Small interfering RNA-mediated depletion of STAT5A significantly impaired anchorage-independent growth of human mammary carcinoma cells, whereas a smaller reduction was observed upon small interfering RNA-mediated depletion of STAT5B. Depletion of endogenous STAT5A also significantly enhanced cell motility, whereas depletion of endogenous STAT5B exhibited no effect. Xenograft studies provided data concordant with the in vitro effects of the two STAT5 isoforms. We therefore demonstrate that STAT5A and STAT5B differentially regulate behavior of human mammary carcinoma cells.

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Signal Transducer and Activator of Transcription (STAT)-A and STAT5B Differentially Regulate Human Mammary Carcinoma Cell Behavior

Endocrine Reviews ◽

10.1210/edrv.30.7.9992 ◽

2009 ◽

Vol 30 (7) ◽

pp. 929-929

Author(s):

Jian-Zhong Tang ◽

Ze-Hua Zuo ◽

Xiang-Jun Kong ◽

Michael Steiner ◽

Zhinan Yin ◽

...

Keyword(s):

Cell Motility ◽

Mammary Carcinoma ◽

Small Interfering Rna ◽

Carcinoma Cells ◽

Migration And Invasion ◽

Signal Transducer ◽

Human Mammary Carcinoma ◽

Anchorage Independent Growth ◽

Mammary Carcinoma Cells ◽

Interfering Rna

Abstract Increased signal transducer and activator of transcription (STAT)-5 activation has been reported in various malignancies including mammary carcinoma. However, it is only recently that potentially distinct roles of STAT5A and STAT5B in neoplasia have begun to emerge. Herein we systematically delineate the functions of STAT5A and STAT5B in human mammary carcinoma cells. Forced expression of constitutively active (CA) STAT5A enhanced both survival and anchorage-independent growth of human mammary carcinoma cells but concordantly suppressed cell motility as revealed in colony scattering, cell migration, and invasion assays. In contrast, forced expression of CA STAT5B exhibited lower potency than CA STAT5A in enhancing survival and anchorage-independent growth of mammary carcinoma cells and exerted no effects on cell motility. Differential expression of genes that regulate cellular survival and motility was concomitantly observed on forced expression of CA STAT5A or CA STAT5B. We also observed that functions of STAT5A and STAT5B were similarly differential in T47D cells. Small interfering RNA-mediated depletion of STAT5A significantly impaired anchorage-independent growth of MCF-7 cells, whereas a smaller reduction was observed upon small interfering RNA-mediated depletion of STAT5B. Depletion of endogenous STAT5A also significantly enhanced cell motility, whereas depletion of endogenous STAT5B exhibited no effect. Xenograft studies provided data concordant with the in vitro effects of the two STAT5 isoforms. We therefore demonstrate that STAT5A and STAT5B differentially regulate behavior of human mammary carcinoma cells.

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ErbB2-overexpressing human mammary carcinoma cells display an increased requirement for the phosphatidylinositol 3-kinase signaling pathway in anchorage-independent growth

Oncogene ◽

10.1038/sj.onc.1204964 ◽

2001 ◽

Vol 20 (51) ◽

pp. 7551-7562 ◽

Cited By ~ 36

Author(s):

Ulrich Hermanto ◽

Cong S Zong ◽

Lu-Hai Wang

Keyword(s):

Signaling Pathway ◽

Mammary Carcinoma ◽

Carcinoma Cells ◽

Kinase Signaling ◽

Phosphatidylinositol 3 Kinase ◽

Human Mammary Carcinoma ◽

Anchorage Independent Growth ◽

Mammary Carcinoma Cells ◽

Kinase Signaling Pathway ◽

Phosphatidylinositol 3

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Rab18 is not necessary for lipid droplet biogenesis or turnover in human mammary carcinoma cells

Molecular Biology of the Cell ◽

10.1091/mbc.e18-05-0282 ◽

2018 ◽

Vol 29 (17) ◽

pp. 2045-2054 ◽

Cited By ~ 18

Author(s):

Christina B. K. Jayson ◽

Henning Arlt ◽

Alexander W. Fischer ◽

Zon Weng Lai ◽

Robert V. Farese ◽

...

Keyword(s):

Mammary Carcinoma ◽

Carcinoma Cells ◽

Effector Protein ◽

Rab Gtpases ◽

Human Mammary Carcinoma ◽

Peripheral Membrane Proteins ◽

Human Mammary Carcinoma Cell ◽

Mammary Carcinoma Cells ◽

And Function ◽

Protein Recruitment

Rab GTPases recruit peripheral membrane proteins and can define organelle identity. Rab18 localizes to the endoplasmic reticulum (ER) but also to lipid droplets (LDs), where it has been implicated in effector protein recruitment and in defining LD identity. Here, we studied Rab18 localization and function in a human mammary carcinoma cell line. Rab18 localized to the ER and to LD membranes on LD induction, with the latter depending on the Rab18 activation state. In cells lacking Rab18, LDs were modestly reduced in size and numbers, but we found little evidence for Rab18 function in LD formation, LD turnover on cell starvation, or the targeting of several proteins to LDs. We conclude that Rab18 is not a general, necessary component of the protein machinery involved in LD biogenesis or turnover.

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