Smoking Linked to Breast Cancer Risk

John (Gold)
John (Gold)

October 17th, 2008, 10:15 pm #11

Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines.
International Journal of Cancer, October 9, 2008 [Epub ahead of print]

Dasgupta P, Rizwani W, Pillai S, Kinkade R, Kovacs M, Rastogi S, Banerjee S, Carless M, Kim E, Coppola D, Haura E, Chellappan S.
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL.

Cigarette smoking is strongly correlated with the onset of nonsmall cell lung cancer (NSCLC). Nicotine, an active component of cigarettes, has been found to induce proliferation of lung cancer cell lines. In addition, nicotine can induce angiogenesis and confer resistance to apoptosis. All these events are mediated through the nicotinic acetylcholine receptors (nAChRs) on lung cancer cells. In this study, we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induces morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the promigratory growth factor VEGF. The proinvasive effects of nicotine were mediated by alpha7-nAChRs on NSCLCs. RT-PCR analysis showed that the alpha7-nAChRs were also expressed on human breast cancer and pancreatic cancer cell lines. Nicotine was found to promote proliferation and invasion in human breast cancer. The proinvasive effects of nicotine were mediated via a nAChR, Src and calcium-dependent signaling pathway in breast cancer cells. In a similar fashion, nicotine could also induce proliferation and invasion of Aspc1 pancreatic cancer cells. Most importantly, nicotine could induce changes in gene expression consistent with epithelial to mesenchymal transition (EMT), characterized by reduction of epithelial markers like E-cadherin expression, ZO-1 staining and concomitant increase in levels of mesenchymal proteins like vimentin and fibronectin in human breast and lung cancer cells. Therefore, it is probable that the ability of nicotine to induce invasion and EMT may contribute to the progression of breast and lung cancers. (c) 2008 Wiley-Liss, Inc.
PMID: 18844224 [PubMed - as supplied by publisher]

Link to Abstract:

Nicotine Promotes Mammary Tumor Migration via a Signaling Cascade Involving Protein Kinase C and cdc42

Cancer Research 68, 8473-8481, October 15, 2008. doi: 10.1158/0008-5472.CAN-08-0131

Jinjin Guo1, Soichiro Ibaragi2, Tongbo Zhu1, Ling-Yu Luo1, Guo-Fu Hu2, Petra S. Huppi3 and Chang Yan Chen1
1 Department of Radiation Oncology, Beth Israel Deaconess Medical Center and 2 Department of Pathology, Harvard Medical School, Boston, Massachusetts and 3 Department of Pediatrics, University of Geneva, Geneva, Switzerland
Requests for reprints: Chang Yan Chen, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 21-27 Burlington Avenue, Room 553C, Boston, MA 02215. Phone: 617-632-8513; Fax: 617-632-0635; E-mail: [][/url] .
Nicotine, one of the major components in tobacco, is at high concentrations in the bloodstream of cigarette smokers. However, the mechanisms of how nicotine affects tumor development and whether nicotine is a potential carcinogen for malignancies induced by secondhand smoking are not fully understood yet. Here, we investigate the signaling pathways by which nicotine potentiates tumorigenesis in human mammary epithelial-like MCF10A or cancerous MCF7 cells. We show that human MCF10A and MCF7 cells both express four subunits of nicotine acetylcholine receptor (nAChR). The treatment of these cells with nicotine enhances the activity of protein kinase C (PKC) [alpha] without altering the expression level of this kinase. Nicotine also stimulates [3H]thymidine incorporation into the genome of these cells as well as forces serum-starved cells to enter S phase of the cell cycle, resulting in growth promotion. Importantly, on nicotine treatment, the mobility of MCF10A and MCF7 cells is enhanced, which can be blocked by the addition of nAChR or PKC inhibitor. Experiments using small interfering RNA knockdown or ectopic expression of cdc42 showed that cdc42 functions as a downstream effector of PKC and is crucial in the regulation of nicotine-mediated migratory activity in the cells. Together, our findings suggest that nicotine, through interacting with its receptor, initiates a signaling cascade that involves PKC and cdc42 and consequently promotes migration in mammary epithelial or tumor cells. ... 68/20/8473

Joined: November 11th, 2008, 7:22 pm

July 29th, 2010, 6:13 pm #12

Researchers find firm link between nicotine, cancer

Thursday, July 29, 2010 -  CNA
TAIPEI -- There is no doubt that smoking or the inhalation of second-hand cigarette smoke can cause breast cancer, Taiwan researchers said yesterday, citing their recent findings in a study on smoking and breast cancer. The study found that a receptor, known as alpha 9 (a9), on breast tissue cells is very sensitive to nicotine.

With a constant nicotine stimulus, the receptor can transform a normal cell into a cancer cell, said professor Ho Yuan-soon of Taipei Medical University's School of Medical Laboratory Science and Biotechnology.

In turn, "the stimulated cell automatically produces more a9," Ho explained. "Gradually the receptor triggers the cell's transformation and the proliferation of a tumor."

When the stimulated cell was planted in the body of laboratory mice with immunodeficiency, cancer cells proliferated rapidly, "as if they were fueled," the researchers said.

The research team then sought to stem the a9 activity by means of gene modification, which resulted in an obvious shrinking of the tumors, Wu said.

The study, which was done on tissue samples from 267 breast cancer patients in Taiwan, found that in the cases of the women who smoked heavily, the a9 receptor was two to three times more active than in those who did not smoke, Wu said.

The more active the a9 receptor, the more aggressive the breast cancer, Wu said.

The study proved a direct link between breast cancer and smoking, the researchers said.

It also located the biomolecule target for the future development of breast cancer cures, according to the research team.

The study will be published in the U.S. journal of the National Cancer Institute on Sept. 8.

Copyright © 1999 – 2010 The China Post.
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July 29th, 2010, 8:24 pm #13

Yikes, it just keeps coming and coming! Thanks for the information.



August 24th, 2010, 11:13 am #14

Nicotine binding to receptor linked to breast cancer cell growth When nicotine binds to the nicotinic acetylcholine receptor (nAchR), it is known to promote smoking addiction and may also directly promote the development of breast cancer, according to a study published online August 23 in The Journal of the National Cancer Institute.

While smoking is a well-known risk factor for a broad range of cancer types, non-nicotine components of tobacco have generally been thought to be the carcinogens, so little is known about how nicotine acts on cells to promote cancer cell growth. For breast cancer in particular, some large epidemiological studies have suggested that smoking is related to increased breast cancer risk, but they have not been accompanied by molecular biology studies on how that actually works.

To determine whether nicotine works on the cellular level to promote breast cancer growth, Yuan-Soon Ho, Ph.D., of the Taipei Medical University, and colleagues, looked at 276 breast tumor samples from anonymous donors to the Taipei Medical University Hospital, to see whether subunits of the nicotinic acetylcholine receptor were overexpressed in breast cancer cells compared with surrounding normal cells.

The researchers found that human breast cancer cells consistently overexpressed the alpha 9 subunit of the nAChR (α9-nAchR), and that expression was higher in advanced-stage breast cancer compared with early-stage cancer. They also found that reducing the levels of α9-nAchRs inhibited tumor growth in laboratory experiments, whereas increasing the levels of α9-nAchRs or treating more normal breast cells with nicotine promoted the development of cancer characteristics.

The authors write: "These results imply that receptor-mediated carcinogenic signals play a decisive role in biological functions related to human breast cancer development."

The authors say their study was limited by its small sample size, and the fact that it included only Asian patients. Breast cancer in Taiwan is characterized by its low incidence rate and early stage of tumor onset.

In an accompanying editorial, Ilona Linnoila, M.D., of the Center for Cancer Research at the National Cancer Institute, writes that the study "suggests not only that smoking could be causally related to breast carcinogenesis but also that nicotine could directly contribute to the molecular mechanism of carcinogenesis in addition to indirectly contributing by promoting addiction to smoking."

Furthermore, Linnoila writes, "Better understanding of the molecular mechanisms of the cholinergic pathways will lead to more opportunities for intervention and prevention of tobacco toxicity."


Article: Yuan-Soon Ho, 011-886-2-27361661 ext 3327, [][/url]
Editorial: Office of Media Relations, the National Cancer Institute, 301-496-6641, [][/url]


Joined: November 11th, 2008, 7:22 pm

October 7th, 2010, 1:09 pm #15

Nicotine linked to breast
cancer risk, study finds

By Dr. Patricia Limpert | Posted: Wednesday, October 6, 2010 2:30 pm

According to a recent Kaiser Family Foundation study, 22.8 percent of Missouri women and 17.5 percent of Illinois women are smokers, which is higher than the national average of 16.2 percent.

And while about 60 percent of those women have attempted to quit at one time or another, they have yet to kick the habit. There are many reasons to stop smoking, but a recent study published in the Journal of the National Cancer Institute may give women another reason not to light up. Researchers have suspected for a long time that smoking increases the risk of breast cancer, but that risk is typically associated with other carcinogens in cigarettes, rather than nicotine. However, this study took a closer look at nicotine specifically, and it found a clear association with breast cancer risk.

The study examined human breast cancer tumors and found the cells had large numbers of receptors which nicotine was able to attach to when compared with normal cells. They also found that when normal cells were treated with nicotine, nicotine promoted the development of cancer characteristics.

Interestingly, the study also found that women who smoke and use hormone replacement therapy containing estrogen and progestins have twice the risk of developing breast cancer compared to nonsmoking women on hormone replacement therapy.

Even if women do not smoke, they still could be putting themselves and their babies at risk. Studies have found women who are exposed to cigarette smoke have nicotine traces in their breast milk. Avoidance of secondhand smoke becomes that much more important for expectant mothers who live or associate with someone who smokes.

These findings only add to other known risks for women who smoke. Those include increased risk of lung cancer, oral cancers, cervical and vulvar cancers, blood clots, high blood pressure, stroke, heart attack, osteoporosis and fractures of the hip and spine, infertility, abnormal menstruation, early onset of menopause and respiratory diseases including asthma and emphysema.

Those who quit smoking experience immediate and long-term benefits including improved circulation, lowered blood pressure and a lower risk of developing cancer as each year passes. For more information on the risks of smoking or to find resources on how to quit, visit

Dr. Patricia Limpert is a breast surgeon at the Breast Care Center at St. Luke's Hospital. Call 314-205-6491 or visit XX Files, a women's health column, rotates each week with Aging Successfully, a column for seniors by Dr. John Morley of St. Louis University.
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Joined: November 11th, 2008, 7:22 pm

January 31st, 2012, 1:09 pm #16

"Quit Quarter" to reduce smoking

Maya Akbay - The Toronto Observer  -  Published 31 January 2012
A Scarborough doctor wants the Royal Canadian Mint’s support in the battle against smoking.

According to Health Canada, smoking remains the number one cause of preventable deaths in Canada. Dr. John Oyston of Scarborough General Hospital hopes to stop the addiction right where it starts – in adolescents.
“Kids don’t see the warning labels, because they never see the packets, they just get single cigarettes off their friends.”     - Dr. John Oyston
He launched a campaign at the start of National No Smoking Week on Jan. 15 to get the Royal Canadian Mint to produce a “Quit Quarter” that is specifically designed to help quit smoking. He hopes a Quit Quarter would especially encourage teenagers getting allowance from their parents to reconsider where they spend their money.

“Kids don’t see the warning labels, because they never see the packets, they just get single cigarettes off their friends,” said Oyston.

“When you start buying cigarettes for yourself, that’s when you’re close to being hooked. At that stage, if you’re digging into your pocket for change and there’s a Quit Quarter there, that’s just another reminder that it all goes back to your health.”

As an anesthesiologist, Oyston sees the damage that smoking does to his patients.

“It’s funny, breast cancer is what people think about when they think of women dying of cancer,” said Oyston. “But more women die from breast cancer due to cigarette smoking than anything else.”

“Maybe in the 50s and 60s, women started smoking and it became acceptable. Now 50 years later, rates for women dying from lung cancer is going up.”

It was the breast cancer awareness coin that sparked the idea in Oyston’s head.

“What’s the purpose of having a coin with a pink ribbon on it? How do you use that to stop getting breast cancer?” Oyston asked.

“You buy cigarettes with money, right?” he added, “So it’s much easier to avoid getting addicted to cigarettes than it is to avoid getting breast cancer.”

The Royal Canadian Mint is “officially thinking about it” while several organizations such as the Canadian Pharmacists Association and the Heart and Stroke Foundation of Ontario have shown their support for the idea.

“I’m just a doctor … If I write to the prime minister, which I did, I don’t get a reply,” said Oyston. “I just need an organization like the Canadian Cancer Society on my side, and a retail chain. So that’s what I’m looking at next.”

What if his teenage son, who pitched a design for the coin himself, started smoking?

“I think the likelihood of that happening is pretty slim!” laughed Oyston. There are no smokers in the family, given the circumstances.
Copyright The Toronto Observer 2012 -  All Rights Reserved
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