Ming-Fong Lin

Professor, Biochemistry and Molecular Biology and Eppley Institute for Cancer

Ming-Fong Lin, PhDPhone: 402-559-6658 (Office)
402-559-6648 (Lab)
Fax: 402-559-6650
Email: mlin@unmc.edu

Education/Training:
Ph.D., State University of New York, Buffalo, 1983

Research:

Student research opportunities in my lab:
Graduate Students
Medical students, summer research
Undergraduate students, summer research

Primary Research/Clinical Interests/Expertise:
Prostate Cancer; Molecular Oncogenesis; Tyrosine Phosphorylation & Dephosphorylation; Redox Signaling; Steroid Hormone Action; Translational Research

Tyrosine phosphorylation and Redox signal transduction in androgen regulation of cell proliferation and carcinogenesis.

Our current effort is to investigate the molecular mechanism of cell growth regulation via tyrosine phosphorylation and Redox signal transduction mediating androgen action for understanding one mechanism of multi-step carcinogenesis of prostate epithelium.

Protein tyrosine phosphorylation by several oncogene proteins and growth factor receptors has been well documented to play a crucial role in the control of cell growth. This is a cyclical process of regulation including phosphorylation and dephosphorylation, which can be regulated at either step. To delineate this cyclical regulatory mechanism, we examine the putative function and regulation of the cellular form of human prostatic acid phosphatase (PAcP), a prostate epithelium-specific protein tyrosine phosphatase. This is because PAcP expression can be regulated by androgens, which is a risk factor for prostate carcinogenesis. Our results show that the expression of cellular PAcP correlates with the androgen responsiveness of human prostate cancer cells. In those cells, cellular PAcP dephosphorylates HER-2/c-ErbB-2/neu proto oncoprotein at specific phosphotyrosine residues. Thus, the interaction of cellular PAcP and ErbB-2 regulates androgen sensitivity of prostate cells. Our recent data further reveal that Redox signaling is mediating the non-genomic androgen stimulated cell proliferation, in part via protein tyrosine phosphorylation signaling. By delineating the molecular mechanism of the cross-talks by tyrosine phosphorylation and Redox signaling mediating androgen action, we will obtain information necessary for a better understanding in some aspects of androgen effects on prostate cancer biology.

To investigate the molecular changes during the progression of prostate cancer cells from androgen-sensitive to advanced androgen-insensitive stages, we have established a U.S. patent-awarded cell model system that recapitulates clinical tumor progression. This model system would allow us to elucidate the molecular mechanism of cancer progression, leading to developing targeted therapies. For immediate clinical applications, we also pursue the development of novel therapeutic approaches applicable for the cases refractory to hormonal therapy of the advanced cancer.

Publications:

Singh, AP, Bafna, S, Chaudhary, K, Venkatraman, G, Smith, L, Eudy, JD, Johansson, SL, Lin, MF, and Batra, SK (2008). Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells. Cancer Letters 259:28-38. Abstract

Veeramani, S, Yuan, TC, Lin, FF, and Lin, MF (2008). Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells. Oncogene 2008; 27:5057-5068. Abstract

Dillard, PR, Lin, MF, and Khan, SA (2008). Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol. Mol Cell Endocrinol 295:115-120. (PMID:1878595) Abstract

Ye CJ, Stevens JB, Liu G, Bremer SW, Jaiswal AS, Ye KJ, Lin MF, Lawrenson L, Lancaster WD, Kurkinen MK, Liao JD, Gairola CG, Shekhar MP, Narayan S, Miller FR, Heng HH. (2009) Genome based cell population heterogeneity promotes tumorigenicity: The evolutionary mechanism of cancer. J Cell Physiol 219(2):2888-300. (PMID:19115235) Abstract

Radhakrishnan P, Lin MF, Cheng PW. (2009) Elevated expression of L-selectin ligand in lymph node-derived human prostate cancer cells correlates with increased tumorigenicity. Glycoconj J. 26(1):75-81. Abstract

Alam S, Rajendran M, Ouyang S, Veeramani S, Li Z, Lin MF. (2009) A novel role of shc adaptor proteins in steroid hormone-regulated cancers. Endocr Relat Cancer. 16:1-16. (PMID:19001530, 2008). Abstract

Zhang L, Davis JS, Zelivianski S, Lin FF, Schutte R, Davis TL, Hauke R, Batra SK, Lin MF. (2009) Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment. Cancer Lett. 285:58-65. (PMID:19467571). Abstract

Veeramani S, Lee MS, Lin MF. (2009) Revisiting histidine-dependent acid phosphatases: A distinct group of tyrosine phosphatases. Trends Biochem Sci. 34:273-278. (PMID:19467874). Abstract

Qin J, Xie Y, Wang B, Hoshino M, Wolff DW, Zhao J, Scofield MA, Dowd FJ, Lin MF, Tu Y. (2009) Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis. Oncogene. 28(16):1853-63. (PMID:19035425)

Rajendran M, Thomes P, Zhang L, Veeramani S, Lin MF. (2010) p66Shc - A longevity redox protein in human prostate cancer progression and metastasis. Cancer Metastasis Rev. 29:207-222. (PMID:20111892)

Chuang TD*, Chen SJ*, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. (2010) Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J. Biological Chemistry (In Press). (PMID:20498373). (*Equal contributions)

Book Chapters/Non Peer-reviewed Articles

Lin MF, Ou-Yang SQ, and Veeramani S. (2009) Comment: "Prostate acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine." Neuron, 9 October 2008, Volume 60, Issue 1, p. 111-122.

Current Grants and Contracts:

DOD Prostate Cancer Synergistic Idea Development Award
Aberrant expression of protein phosphatases during androgen-independent growth in human prostate cancer cells 
Principal Investigator: Ming-Fong Lin, Ph.D.
Co-Principal Investigator: Surinder K. Batra, Ph.D.
7/15/2008 - 7/14/2012

National Cancer Institute
Signaling in Androgen-Refractory Prostate Cancer 
Principal Investigator: Ming-Fong Lin, Ph.D.
8/1/2006 - 7/31/2012

National Institutes of Health, National Cancer Institute
Regulator of G-protein Signaling (RGS) Proteins in Prostate Cancer
Principal Investigator: Yaping Tu, Ph.D. (Creighton University)
Co-Investigator: Ming-Fong Lin, Ph.D.
10/1/2007 - 9/30/2012

National Cancer Institute, National Institutes of Health
Cancer Biology Training Grant
Principal Investigator: Angie Rizzino, Ph.D. (Eppley Cancer Institute)
Co-Investigators/Mentors: Ming-Fong Lin, Ph.D. and Eppley Cancer Center Members
7/1/2008 - 6/30/2013

DHHS/NIH/NCI
Novel Deregulated Genes in the Etiology and Progression of Human Prostate Cancer
Principal Investigator: Surinder Batra, Ph.D.
Co-Investigator: Ming-Fong Lin, Ph.D.
5/1/2010 - 4/30/2015

DOD PCRP of CDMRP, Collaborative Undergraduate HBCU Student Summer Training Program Award
Nebraska Prostate Cancer Research Program
Principal Investigator: Ming-Fong Lin, Ph.D.
4/20/2010 - 4/19/2013

National Institutes of Health
p53 Mediated Apoptotic Pathways in Renal Ischemia
8/1/2010 - 7/31/2015

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