J Cancer 2013; 4(7):566-572. doi:10.7150/jca.6638 This issue

Research Paper

TGF-β2: A Novel Target of CD44-Promoted Breast Cancer Invasion

Allal Ouhtit1✉, Samineh Madani1, Ishita Gupta1, Somya Shanmuganathan1, Mohamed E. Abdraboh3, Hamad Al-Riyami1, Yahya M Al-Farsi2, Madhwa HG Raj3

1. Department of Genetics,
2. Department of Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate Of Oman
3. Department of Ob GYN, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA

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Ouhtit A, Madani S, Gupta I, Shanmuganathan S, Abdraboh ME, Al-Riyami H, Al-Farsi YM, Raj MHG. TGF-β2: A Novel Target of CD44-Promoted Breast Cancer Invasion. J Cancer 2013; 4(7):566-572. doi:10.7150/jca.6638. Available from https://www.jcancer.org/v04p0566.htm

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We have developed a tetracycline (tet)-off regulated expression of CD44s gene in the breast cancer (BC) cell line MCF-7 (B5 clone) and identified TGF-β2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44-downstream transcriptional target by microarray analysis. To further validate this finding, the same RNA samples, used for microarray analysis and their corresponding protein lysates, collected from the BC cell line MCF-7-B5, were examined for CD44 expression in the presence of HA. Our results showed that TGF-β2 mRNA levels were significantly elevated following the removal of tetracycline at 18, 24, and 48 h post-HA stimulation compared to the parental cells. Furthermore, the TGF-β2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tetracycline. More interestingly, inhibition of CD44 gene by RNAi method decreased TGF-β2 expression upon HA-stimulation, and subsequently inhibited BC cell invasion in vitro. In addition to identifying TGF-β2 as a target for HA/CD44 signaling, this data suggests that ATF/CREB might be a potential transcription factor linking HA/CD44 activation to TGF-β2 transcription and additional experiments are required for a better understanding of the molecular mechanisms underpinning the novel function of the CD44/ TGF-β2 signaling pathway in breast cancer metastasis.

Keywords: Hyaluronan, CD44, TGF-β2, CRE/ATF, Tetracycline-inducible, Breast cancer, Metastasis, MCF-7-B5 clone